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3
INTRODUCTION
1
13
[ "B13", "B15", "B16", "B10", "B22", "B20", "B23", "B21", "B23", "B12", "B13", "B21" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
Therefore, the possibility cannot be ruled out that DME, ROS1 and/or DML3 also play a role in repairing T:G mismatches arising from spontaneous deamination of 5-meC to thymine.
[ "13", "15", "16", "10", "22", "20", "23", "21", "23", "12", "13", "21" ]
176
40,516
0
false
Therefore, the possibility cannot be ruled out that DME, ROS1 and/or DML3 also play a role in repairing T:G mismatches arising from spontaneous deamination of 5-meC to thymine.
[]
Therefore, the possibility cannot be ruled out that DME, ROS1 and/or DML3 also play a role in repairing T:G mismatches arising from spontaneous deamination of 5-meC to thymine.
true
true
true
true
true
6,991
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
Discovering the molecular details of events involved in processing target bases by enzymes of the ROS1/DME family will be important to our understanding of the biological functions and relevance of these proteins.
[ "24", "25" ]
213
40,517
0
false
Discovering the molecular details of events involved in processing target bases by enzymes of the ROS1/DME family will be important to our understanding of the biological functions and relevance of these proteins.
[]
Discovering the molecular details of events involved in processing target bases by enzymes of the ROS1/DME family will be important to our understanding of the biological functions and relevance of these proteins.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
It remains unknown how the enzymes of the ROS1/DME family specifically recognize 5-meC in DNA and distinguish it from unmethylated C. A methylated cytosine is not a damaged base, but its effects on DNA structure are not yet completely understood.
[ "24", "25" ]
246
40,518
0
false
It remains unknown how the enzymes of the ROS1/DME family specifically recognize 5-meC in DNA and distinguish it from unmethylated C. A methylated cytosine is not a damaged base, but its effects on DNA structure are not yet completely understood.
[]
It remains unknown how the enzymes of the ROS1/DME family specifically recognize 5-meC in DNA and distinguish it from unmethylated C. A methylated cytosine is not a damaged base, but its effects on DNA structure are not yet completely understood.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
Some of them may involve subtle conformational changes, since it has been reported that the methyl group at C5 of cytosine induces a slight displacement of the surrounding bases to the minor groove of the helix, making it shallower (24,25).
[ "24", "25" ]
240
40,519
0
false
Some of them may involve subtle conformational changes, since it has been reported that the methyl group at C5 of cytosine induces a slight displacement of the surrounding bases to the minor groove of the helix, making it shallower.
[ "24,25" ]
Some of them may involve subtle conformational changes, since it has been reported that the methyl group at C5 of cytosine induces a slight displacement of the surrounding bases to the minor groove of the helix, making it shallower.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
A complete understanding of how plant 5-meC DNA glycosylases recognize and excise target bases will require a thorough examination of their biochemical characteristics.
[ "24", "25" ]
168
40,520
0
false
A complete understanding of how plant 5-meC DNA glycosylases recognize and excise target bases will require a thorough examination of their biochemical characteristics.
[]
A complete understanding of how plant 5-meC DNA glycosylases recognize and excise target bases will require a thorough examination of their biochemical characteristics.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
In this study we have analysed the substrate specificity and functional properties of ROS1.
[ "24", "25" ]
91
40,521
0
false
In this study we have analysed the substrate specificity and functional properties of ROS1.
[]
In this study we have analysed the substrate specificity and functional properties of ROS1.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
We report that the nature of the substituent group at C5 of the target base has a major impact on defining the substrate specificity of ROS1 and that the identity of the opposite base affects 5-meC and T excision differently.
[ "24", "25" ]
225
40,522
0
false
We report that the nature of the substituent group at C5 of the target base has a major impact on defining the substrate specificity of ROS1 and that the identity of the opposite base affects 5-meC and T excision differently.
[]
We report that the nature of the substituent group at C5 of the target base has a major impact on defining the substrate specificity of ROS1 and that the identity of the opposite base affects 5-meC and T excision differently.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
We also found that ROS1 binds to the abasic (apurinic/apyrimidinic, AP) site intermediate generated during the reaction.
[ "24", "25" ]
120
40,523
0
false
We also found that ROS1 binds to the abasic (apurinic/apyrimidinic, AP) site intermediate generated during the reaction.
[]
We also found that ROS1 binds to the abasic (apurinic/apyrimidinic, AP) site intermediate generated during the reaction.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
This binding leads to a highly distributive behaviour on DNA substrates containing several 5-meC residues, and may help to avoid generation of double-strand breaks as bimethylated CG sites are processed.
[ "24", "25" ]
203
40,524
0
false
This binding leads to a highly distributive behaviour on DNA substrates containing several 5-meC residues, and may help to avoid generation of double-strand breaks as bimethylated CG sites are processed.
[]
This binding leads to a highly distributive behaviour on DNA substrates containing several 5-meC residues, and may help to avoid generation of double-strand breaks as bimethylated CG sites are processed.
true
true
true
true
true
6,992
4
INTRODUCTION
1
24
[ "B24", "B25" ]
19,443,451
pmid-1559976|pmid-10518799
We discuss these functional properties in the light of the possible in vivo functions of ROS1.
[ "24", "25" ]
94
40,525
0
false
We discuss these functional properties in the light of the possible in vivo functions of ROS1.
[]
We discuss these functional properties in the light of the possible in vivo functions of ROS1.
true
true
true
true
true
6,992
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
A central issue in base excision repair is how DNA glycosylases recognize specific types of bases and discriminate against non-target substrates.
[ "12", "38–40", "41", "39", "39", "40" ]
145
40,526
0
false
A central issue in base excision repair is how DNA glycosylases recognize specific types of bases and discriminate against non-target substrates.
[]
A central issue in base excision repair is how DNA glycosylases recognize specific types of bases and discriminate against non-target substrates.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
ROS1 displays the remarkable capacity to excise 5-meC and T while retaining the ability to discriminate effectively against C and U (12).
[ "12", "38–40", "41", "39", "39", "40" ]
137
40,527
1
false
ROS1 displays the remarkable capacity to excise 5-meC and T while retaining the ability to discriminate effectively against C and U.
[ "12" ]
ROS1 displays the remarkable capacity to excise 5-meC and T while retaining the ability to discriminate effectively against C and U.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
This suggests that the enzyme makes specific contacts with the methyl group at C5 of the target base.
[ "12", "38–40", "41", "39", "39", "40" ]
101
40,528
0
false
This suggests that the enzyme makes specific contacts with the methyl group at C5 of the target base.
[]
This suggests that the enzyme makes specific contacts with the methyl group at C5 of the target base.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
In this work we examined ROS1 activity on several 5-substituted derivatives of C and T. We found that substitution of the methyl group of thymine by OH actually increased enzymatic activity, while the introduction of a bulkier substituent, such as CH2OH, virtually abolished it.
[ "12", "38–40", "41", "39", "39", "40" ]
278
40,529
0
false
In this work we examined ROS1 activity on several 5-substituted derivatives of C and T. We found that substitution of the methyl group of thymine by OH actually increased enzymatic activity, while the introduction of a bulkier substituent, such as CH2OH, virtually abolished it.
[]
In this work we examined ROS1 activity on several 5-substituted derivatives of C and T. We found that substitution of the methyl group of thymine by OH actually increased enzymatic activity, while the introduction of a bulkier substituent, such as CH2OH, virtually abolished it.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
On the other hand, replacement of the methyl group by halogen substituents Br or F substantially decreased excision of the target base.
[ "12", "38–40", "41", "39", "39", "40" ]
135
40,530
0
false
On the other hand, replacement of the methyl group by halogen substituents Br or F substantially decreased excision of the target base.
[]
On the other hand, replacement of the methyl group by halogen substituents Br or F substantially decreased excision of the target base.
true
true
true
true
true
6,993
0
DISCUSSION
1
38–40
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
It should be noted that this substrate preference contrasts strikingly with that of other thymine glycosylases, such as TDG (38–40) and MBD4 (41), which show higher activity with uracil and its halogenated derivatives.
[ "12", "38–40", "41", "39", "39", "40" ]
218
40,531
1
false
It should be noted that this substrate preference contrasts strikingly with that of other thymine glycosylases, such as TDG and MBD4, which show higher activity with uracil and its halogenated derivatives.
[ "38–40", "41" ]
It should be noted that this substrate preference contrasts strikingly with that of other thymine glycosylases, such as TDG and MBD4, which show higher activity with uracil and its halogenated derivatives.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
This preference has been explained in terms of substrate reactivity.
[ "12", "38–40", "41", "39", "39", "40" ]
68
40,532
0
false
This preference has been explained in terms of substrate reactivity.
[]
This preference has been explained in terms of substrate reactivity.
true
true
true
true
true
6,993
0
DISCUSSION
1
39
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
Electron-withdrawing substituents, such as Br or F, stabilize the transition state and enhance the leaving ability of the base, while electron-donating groups, such as CH3, actually destabilize the transition state and may slow the reaction (39).
[ "12", "38–40", "41", "39", "39", "40" ]
246
40,533
1
false
Electron-withdrawing substituents, such as Br or F, stabilize the transition state and enhance the leaving ability of the base, while electron-donating groups, such as CH3, actually destabilize the transition state and may slow the reaction.
[ "39" ]
Electron-withdrawing substituents, such as Br or F, stabilize the transition state and enhance the leaving ability of the base, while electron-donating groups, such as CH3, actually destabilize the transition state and may slow the reaction.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
At least in the case of TDG, this has led to the proposal that specificity depends on the stability of the scissile C–N bond rather than the selective recognition of substrates at the active site (39,40).
[ "12", "38–40", "41", "39", "39", "40" ]
204
40,534
0
false
At least in the case of TDG, this has led to the proposal that specificity depends on the stability of the scissile C–N bond rather than the selective recognition of substrates at the active site.
[ "39,40" ]
At least in the case of TDG, this has led to the proposal that specificity depends on the stability of the scissile C–N bond rather than the selective recognition of substrates at the active site.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
In the case of ROS1, increasing leaving ability of the target base does not overcome the negative effect of the substituents on excision efficiency.
[ "12", "38–40", "41", "39", "39", "40" ]
148
40,535
0
false
In the case of ROS1, increasing leaving ability of the target base does not overcome the negative effect of the substituents on excision efficiency.
[]
In the case of ROS1, increasing leaving ability of the target base does not overcome the negative effect of the substituents on excision efficiency.
true
true
true
true
true
6,993
0
DISCUSSION
1
12
[ "B12", "B38 B39 B40", "B41", "B39", "B39", "B40" ]
19,443,451
pmid-15952895|pmid-17320505|pmid-17522675|pmid-11782440|pmid-11498573|pmid-11498574|pmid-11262868|pmid-17339880|NA|pmid-12526807|pmid-12150995|pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-12711670|pmid-16984202|pmid-17602166|pmid-16885370|pmid-16984202|pmid-16984202|pmid-17602166
Thus, our results suggest that ROS1 may rather specifically recognize 5-meC and T by selective steric and/or electrostatic interactions involving the methyl group at position C5.
[ "12", "38–40", "41", "39", "39", "40" ]
178
40,536
0
false
Thus, our results suggest that ROS1 may rather specifically recognize 5-meC and T by selective steric and/or electrostatic interactions involving the methyl group at position C5.
[]
Thus, our results suggest that ROS1 may rather specifically recognize 5-meC and T by selective steric and/or electrostatic interactions involving the methyl group at position C5.
true
true
true
true
true
6,993
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
We also examined the effect of pairing the target base with C, T or A, rather than G, and found entirely different effects on the capacity of ROS1 to excise 5-meC and T. 5-meC was excised less efficiently when correctly paired with G than when mispaired with any of the other three bases.
[ "42", "43", "32", "44", "33" ]
288
40,537
0
false
We also examined the effect of pairing the target base with C, T or A, rather than G, and found entirely different effects on the capacity of ROS1 to excise 5-meC and T. 5-meC was excised less efficiently when correctly paired with G than when mispaired with any of the other three bases.
[]
We also examined the effect of pairing the target base with C, T or A, rather than G, and found entirely different effects on the capacity of ROS1 to excise 5-meC and T. 5-meC was excised less efficiently when correctly paired with G than when mispaired with any of the other three bases.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
It is possible that processing mismatched 5-meC is biologically relevant in vivo.
[ "42", "43", "32", "44", "33" ]
81
40,538
0
false
It is possible that processing mismatched 5-meC is biologically relevant in vivo.
[]
It is possible that processing mismatched 5-meC is biologically relevant in vivo.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
It has been reported that DNA methyltransferases can efficiently catalyse methylation of mismatched C in vitro (42,43).
[ "42", "43", "32", "44", "33" ]
119
40,539
0
false
It has been reported that DNA methyltransferases can efficiently catalyse methylation of mismatched C in vitro.
[ "42,43" ]
It has been reported that DNA methyltransferases can efficiently catalyse methylation of mismatched C in vitro.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
A methylated C in a mismatch may also arise from the erroneous insertion of an incoming nucleotide opposite 5-meC during DNA replication.
[ "42", "43", "32", "44", "33" ]
137
40,540
0
false
A methylated C in a mismatch may also arise from the erroneous insertion of an incoming nucleotide opposite 5-meC during DNA replication.
[]
A methylated C in a mismatch may also arise from the erroneous insertion of an incoming nucleotide opposite 5-meC during DNA replication.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
In both scenarios, ROS1 activity could lead to mutations if 5-meC is the correct base in the mispair, because it would initiate its incorrect removal.
[ "42", "43", "32", "44", "33" ]
150
40,541
0
false
In both scenarios, ROS1 activity could lead to mutations if 5-meC is the correct base in the mispair, because it would initiate its incorrect removal.
[]
In both scenarios, ROS1 activity could lead to mutations if 5-meC is the correct base in the mispair, because it would initiate its incorrect removal.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
However, it is perhaps more likely that the efficient processing of mismatched 5-meC by ROS1 in vitro simply reflects the reduced thermodynamic stability of 5-meC mispairs compared with a correct 5-meC:G pair.
[ "42", "43", "32", "44", "33" ]
209
40,542
0
false
However, it is perhaps more likely that the efficient processing of mismatched 5-meC by ROS1 in vitro simply reflects the reduced thermodynamic stability of 5-meC mispairs compared with a correct 5-meC:G pair.
[]
However, it is perhaps more likely that the efficient processing of mismatched 5-meC by ROS1 in vitro simply reflects the reduced thermodynamic stability of 5-meC mispairs compared with a correct 5-meC:G pair.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
In contrast to 5-meC excision specificity, we found that ROS1 only excised T when mispaired with G, whereas no detectable activity was observed with either T:A, T:T or T:C. This strict preference may be rationalized in terms of the possible consequences of each excision event in vivo.
[ "42", "43", "32", "44", "33" ]
285
40,543
0
false
In contrast to 5-meC excision specificity, we found that ROS1 only excised T when mispaired with G, whereas no detectable activity was observed with either T:A, T:T or T:C. This strict preference may be rationalized in terms of the possible consequences of each excision event in vivo.
[]
In contrast to 5-meC excision specificity, we found that ROS1 only excised T when mispaired with G, whereas no detectable activity was observed with either T:A, T:T or T:C. This strict preference may be rationalized in terms of the possible consequences of each excision event in vivo.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
The failure to excise thymine when correctly paired with A suggests that the enzyme has an effective mechanism for avoiding activity on the huge excess of normal T:A pairs in DNA.
[ "42", "43", "32", "44", "33" ]
179
40,544
0
false
The failure to excise thymine when correctly paired with A suggests that the enzyme has an effective mechanism for avoiding activity on the huge excess of normal T:A pairs in DNA.
[]
The failure to excise thymine when correctly paired with A suggests that the enzyme has an effective mechanism for avoiding activity on the huge excess of normal T:A pairs in DNA.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
On the other hand, the absence of activity with T:T or T:C mispairs may avoid potential fixation of DNA replication errors into mutations due to the presumed inability of ROS1 to distinguish the erroneous base.
[ "42", "43", "32", "44", "33" ]
210
40,545
0
false
On the other hand, the absence of activity with T:T or T:C mispairs may avoid potential fixation of DNA replication errors into mutations due to the presumed inability of ROS1 to distinguish the erroneous base.
[]
On the other hand, the absence of activity with T:T or T:C mispairs may avoid potential fixation of DNA replication errors into mutations due to the presumed inability of ROS1 to distinguish the erroneous base.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
This extreme preference for G as a pairing partner for the substrate T is analogous to that observed for other thymine DNA glycosylases.
[ "42", "43", "32", "44", "33" ]
136
40,546
0
false
This extreme preference for G as a pairing partner for the substrate T is analogous to that observed for other thymine DNA glycosylases.
[]
This extreme preference for G as a pairing partner for the substrate T is analogous to that observed for other thymine DNA glycosylases.
true
true
true
true
true
6,994
1
DISCUSSION
1
42
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
Thus, the rate of T removal by TDG from T:G mismatches is 1–2 orders of magnitude higher than that from T:C or T:T mismatches, and no activity on T:A pairs has been detected (32,44).
[ "42", "43", "32", "44", "33" ]
182
40,547
0
false
Thus, the rate of T removal by TDG from T:G mismatches is 1–2 orders of magnitude higher than that from T:C or T:T mismatches, and no activity on T:A pairs has been detected.
[ "32,44" ]
Thus, the rate of T removal by TDG from T:G mismatches is 1–2 orders of magnitude higher than that from T:C or T:T mismatches, and no activity on T:A pairs has been detected.
true
true
true
true
true
6,994
1
DISCUSSION
1
33
[ "B42", "B43", "B32", "B44", "B33" ]
19,443,451
pmid-12526807|pmid-12150995|pmid-14631047|pmid-16648367|pmid-12150995|pmid-8805338|pmid-12832627|NA|pmid-7753630|pmid-3658670|pmid-9685338|pmid-8407958|pmid-10930409
Similarly, no MBD4 activity has been detected on either T:T, T:C or T:A pairs (33).
[ "42", "43", "32", "44", "33" ]
83
40,548
1
false
Similarly, no MBD4 activity has been detected on either T:T, T:C or T:A pairs.
[ "33" ]
Similarly, no MBD4 activity has been detected on either T:T, T:C or T:A pairs.
true
true
true
true
true
6,994
2
DISCUSSION
1
45
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
In rationalizing the contrasting effects of opposite residues on 5-meC and T excision it must be remembered that the substrate specificity of DNA glycosylases is shaped by natural selection driven only by the base pairs and mispairs likely to be encountered in cells (45).
[ "45", "46" ]
272
40,549
1
false
In rationalizing the contrasting effects of opposite residues on 5-meC and T excision it must be remembered that the substrate specificity of DNA glycosylases is shaped by natural selection driven only by the base pairs and mispairs likely to be encountered in cells.
[ "45" ]
In rationalizing the contrasting effects of opposite residues on 5-meC and T excision it must be remembered that the substrate specificity of DNA glycosylases is shaped by natural selection driven only by the base pairs and mispairs likely to be encountered in cells.
true
true
true
true
true
6,995
2
DISCUSSION
1
45
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
ROS1 avoids mutagenic excision of T from normal T:A pairs and also from T:C and T:T mispairs.
[ "45", "46" ]
93
40,550
0
false
ROS1 avoids mutagenic excision of T from normal T:A pairs and also from T:C and T:T mispairs.
[]
ROS1 avoids mutagenic excision of T from normal T:A pairs and also from T:C and T:T mispairs.
true
true
true
true
true
6,995
2
DISCUSSION
1
45
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
However, it is not precluded from excising 5-meC from thermodynamically unstable 5-meC mispairs, probably because they are very rarely encountered by the enzyme in vivo.
[ "45", "46" ]
169
40,551
0
false
However, it is not precluded from excising 5-meC from thermodynamically unstable 5-meC mispairs, probably because they are very rarely encountered by the enzyme in vivo.
[]
However, it is not precluded from excising 5-meC from thermodynamically unstable 5-meC mispairs, probably because they are very rarely encountered by the enzyme in vivo.
true
true
true
true
true
6,995
2
DISCUSSION
1
45
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
Something similar has been observed with E. coli Fpg, which removes 8-oxoguanine residues from DNA.
[ "45", "46" ]
99
40,552
0
false
Something similar has been observed with E. coli Fpg, which removes 8-oxoguanine residues from DNA.
[]
Something similar has been observed with E. coli Fpg, which removes 8-oxoguanine residues from DNA.
true
true
true
true
true
6,995
2
DISCUSSION
1
46
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
Excision of 8-oxoG from the uncommon 8-oxoG:G and 8-oxoG:T mispairs is 10–30 times faster than from 8-oxoG:C, but the enzyme effectively avoids excision from the frequent 8-oxoG:A pairs generated by erroneous 8-oxoG replication (46).
[ "45", "46" ]
233
40,553
1
false
Excision of 8-oxoG from the uncommon 8-oxoG:G and 8-oxoG:T mispairs is 10–30 times faster than from 8-oxoG:C, but the enzyme effectively avoids excision from the frequent 8-oxoG:A pairs generated by erroneous 8-oxoG replication.
[ "46" ]
Excision of 8-oxoG from the uncommon 8-oxoG:G and 8-oxoG:T mispairs is 10–30 times faster than from 8-oxoG:C, but the enzyme effectively avoids excision from the frequent 8-oxoG:A pairs generated by erroneous 8-oxoG replication.
true
true
true
true
true
6,995
2
DISCUSSION
1
45
[ "B45", "B46" ]
19,443,451
pmid-16624880|pmid-16469697|pmid-16864782|pmid-16624880|pmid-16624880|pmid-16469697|pmid-16624880|pmid-16469697|pmid-16624880|pmid-18278030|pmid-17409185|pmid-18493721|pmid-17409185|pmid-18493721|pmid-15939442|pmid-7515054
Nevertheless, a comprehensive mechanistic explanation of ROS1 specificity will require detailed kinetic and structural information.
[ "45", "46" ]
131
40,554
0
false
Nevertheless, a comprehensive mechanistic explanation of ROS1 specificity will require detailed kinetic and structural information.
[]
Nevertheless, a comprehensive mechanistic explanation of ROS1 specificity will require detailed kinetic and structural information.
true
true
true
true
true
6,995
3
DISCUSSION
1
28
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
We have examined the DNA glycosylase activity of ROS1 separately from its AP lyase activity, and found that 5-meC excision and AP incision are concurrent.
[ "28", "12", "47", "29", "30" ]
154
40,555
0
false
We have examined the DNA glycosylase activity of ROS1 separately from its AP lyase activity, and found that 5-meC excision and AP incision are concurrent.
[]
We have examined the DNA glycosylase activity of ROS1 separately from its AP lyase activity, and found that 5-meC excision and AP incision are concurrent.
true
true
true
true
true
6,996
3
DISCUSSION
1
28
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
The factors determining the coupling or dissociation of glycosylase and lyase activities are not yet understood.
[ "28", "12", "47", "29", "30" ]
112
40,556
0
false
The factors determining the coupling or dissociation of glycosylase and lyase activities are not yet understood.
[]
The factors determining the coupling or dissociation of glycosylase and lyase activities are not yet understood.
true
true
true
true
true
6,996
3
DISCUSSION
1
28
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
The unified mechanism proposed for bifunctional DNA glycosylases postulates coordination of base excision and beta-elimination as a result of Schiff base formation (28).
[ "28", "12", "47", "29", "30" ]
169
40,557
1
false
The unified mechanism proposed for bifunctional DNA glycosylases postulates coordination of base excision and beta-elimination as a result of Schiff base formation.
[ "28" ]
The unified mechanism proposed for bifunctional DNA glycosylases postulates coordination of base excision and beta-elimination as a result of Schiff base formation.
true
true
true
true
true
6,996
3
DISCUSSION
1
12
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
We have previously reported that excision of 5-meC by both ROS1 and DME proceeds via a Schiff base (12).
[ "28", "12", "47", "29", "30" ]
104
40,558
1
false
We have previously reported that excision of 5-meC by both ROS1 and DME proceeds via a Schiff base.
[ "12" ]
We have previously reported that excision of 5-meC by both ROS1 and DME proceeds via a Schiff base.
true
true
true
true
true
6,996
3
DISCUSSION
1
47
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
In other bifunctional DNA glycosylases, such as E. coli 8-oxoG DNA glycosylase Fpg, base excision is also tightly coupled with DNA strand cleavage (47).
[ "28", "12", "47", "29", "30" ]
152
40,559
1
false
In other bifunctional DNA glycosylases, such as E. coli 8-oxoG DNA glycosylase Fpg, base excision is also tightly coupled with DNA strand cleavage.
[ "47" ]
In other bifunctional DNA glycosylases, such as E. coli 8-oxoG DNA glycosylase Fpg, base excision is also tightly coupled with DNA strand cleavage.
true
true
true
true
true
6,996
3
DISCUSSION
1
28
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
However, not all bifunctional DNA glycosylases involve coupling of excision and incision.
[ "28", "12", "47", "29", "30" ]
89
40,560
0
false
However, not all bifunctional DNA glycosylases involve coupling of excision and incision.
[]
However, not all bifunctional DNA glycosylases involve coupling of excision and incision.
true
true
true
true
true
6,996
3
DISCUSSION
1
28
[ "B28", "B12", "B47", "B29", "B30" ]
19,443,451
pmid-16469697|pmid-14631047|pmid-16648367|pmid-12526807|pmid-17208187|pmid-17409185|pmid-18423832|pmid-18493721|pmid-18423832|pmid-16624880|pmid-16469697|pmid-18493721|pmid-7806489|pmid-16624880|pmid-18154319|pmid-11287425|pmid-10884383
Thus, human Endonuclease III (hNTH1) and mammalian OGG1 display a significant dissociation of the two activities, with the rate of AP lyase-mediated strand cleavage being significantly slower than the glycosylase-mediated base excision (29,30).
[ "28", "12", "47", "29", "30" ]
244
40,561
0
false
Thus, human Endonuclease III (hNTH1) and mammalian OGG1 display a significant dissociation of the two activities, with the rate of AP lyase-mediated strand cleavage being significantly slower than the glycosylase-mediated base excision.
[ "29,30" ]
Thus, human Endonuclease III (hNTH1) and mammalian OGG1 display a significant dissociation of the two activities, with the rate of AP lyase-mediated strand cleavage being significantly slower than the glycosylase-mediated base excision.
true
true
true
true
true
6,996
4
DISCUSSION
0
null
null
19,443,451
pmid-1559976|pmid-10518799
We investigated the time-course of 5-meC excision and found that the product accumulated biphasically, with an initial burst whose amplitude was correlated with the amount of enzyme used.
null
187
40,562
0
false
null
null
We investigated the time-course of 5-meC excision and found that the product accumulated biphasically, with an initial burst whose amplitude was correlated with the amount of enzyme used.
true
true
true
true
true
6,997
4
DISCUSSION
0
null
null
19,443,451
pmid-1559976|pmid-10518799
Furthermore, we confirmed that the amount of enzyme effectively limited the amount of product generated in the reaction, and that ROS1 removed a near-stoichiometric quantity of 5-meC.
null
183
40,563
0
false
null
null
Furthermore, we confirmed that the amount of enzyme effectively limited the amount of product generated in the reaction, and that ROS1 removed a near-stoichiometric quantity of 5-meC.
true
true
true
true
true
6,997
4
DISCUSSION
0
null
null
19,443,451
pmid-1559976|pmid-10518799
The reason for this behaviour is that the turnover of the enzyme was exceedingly low, since it binds strongly to the AP site generated after 5-meC excision.
null
156
40,564
0
false
null
null
The reason for this behaviour is that the turnover of the enzyme was exceedingly low, since it binds strongly to the AP site generated after 5-meC excision.
true
true
true
true
true
6,997
5
DISCUSSION
1
31–34
[ "B31 B32 B33 B34" ]
19,443,451
pmid-11238994|pmid-9685338|pmid-10930409|pmid-12519758
These results suggest that, as previously described for other DNA glycosylases (31–34), the rate-limiting step in the action of ROS1 occurs after base excision.
[ "31–34" ]
160
40,565
1
false
These results suggest that, as previously described for other DNA glycosylases, the rate-limiting step in the action of ROS1 occurs after base excision.
[ "31–34" ]
These results suggest that, as previously described for other DNA glycosylases, the rate-limiting step in the action of ROS1 occurs after base excision.
true
true
true
true
true
6,998
5
DISCUSSION
1
31–34
[ "B31 B32 B33 B34" ]
19,443,451
pmid-11238994|pmid-9685338|pmid-10930409|pmid-12519758
Given the coupling between base excision and strand incision, our findings imply that, in most cases, ROS1 does not dissociate from the AP site intermediate and engages in the AP lyase reaction.
[ "31–34" ]
194
40,566
0
false
Given the coupling between base excision and strand incision, our findings imply that, in most cases, ROS1 does not dissociate from the AP site intermediate and engages in the AP lyase reaction.
[]
Given the coupling between base excision and strand incision, our findings imply that, in most cases, ROS1 does not dissociate from the AP site intermediate and engages in the AP lyase reaction.
true
true
true
true
true
6,998
5
DISCUSSION
1
31–34
[ "B31 B32 B33 B34" ]
19,443,451
pmid-11238994|pmid-9685338|pmid-10930409|pmid-12519758
Such a restraint at the expense of turnover probably reflects an essential coordination with enzymes acting on subsequent steps in the base excision pathway, thus assuring protection of the potentially harmful AP site that arises during the reaction.
[ "31–34" ]
250
40,567
0
false
Such a restraint at the expense of turnover probably reflects an essential coordination with enzymes acting on subsequent steps in the base excision pathway, thus assuring protection of the potentially harmful AP site that arises during the reaction.
[]
Such a restraint at the expense of turnover probably reflects an essential coordination with enzymes acting on subsequent steps in the base excision pathway, thus assuring protection of the potentially harmful AP site that arises during the reaction.
true
true
true
true
true
6,998
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
Avoiding hazardous reaction intermediates may be particularly important in the case of ROS1, because simultaneous excision on bimethylated CG sites could generate deleterious double-strand breaks.
[ "13", "48", "49" ]
196
40,568
0
false
Avoiding hazardous reaction intermediates may be particularly important in the case of ROS1, because simultaneous excision on bimethylated CG sites could generate deleterious double-strand breaks.
[]
Avoiding hazardous reaction intermediates may be particularly important in the case of ROS1, because simultaneous excision on bimethylated CG sites could generate deleterious double-strand breaks.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
We found that, even after extended incubation, ROS1 did not produce detectable levels of DSB on a DNA substrate containing a bimethylated CG site.
[ "13", "48", "49" ]
146
40,569
0
false
We found that, even after extended incubation, ROS1 did not produce detectable levels of DSB on a DNA substrate containing a bimethylated CG site.
[]
We found that, even after extended incubation, ROS1 did not produce detectable levels of DSB on a DNA substrate containing a bimethylated CG site.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
This suggests that 5-meC excision in one strand efficiently prevents processing of the methylated cytosine in the complementary strand.
[ "13", "48", "49" ]
135
40,570
0
false
This suggests that 5-meC excision in one strand efficiently prevents processing of the methylated cytosine in the complementary strand.
[]
This suggests that 5-meC excision in one strand efficiently prevents processing of the methylated cytosine in the complementary strand.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
It has been reported that the activity of the ROS1-related enzyme DME on a hemimethylated CG site is inhibited by about 10-fold by the presence of an AP site on the opposite strand (13).
[ "13", "48", "49" ]
186
40,571
1
false
It has been reported that the activity of the ROS1-related enzyme DME on a hemimethylated CG site is inhibited by about 10-fold by the presence of an AP site on the opposite strand.
[ "13" ]
It has been reported that the activity of the ROS1-related enzyme DME on a hemimethylated CG site is inhibited by about 10-fold by the presence of an AP site on the opposite strand.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
Our results suggest that in the case of ROS1 it is unlikely that this circumstance actually occurs in vivo, and it is more probable that the glycosylase will prevent processing of the opposite strand by strongly binding to the AP site until the next step in the excision pathway.
[ "13", "48", "49" ]
279
40,572
0
false
Our results suggest that in the case of ROS1 it is unlikely that this circumstance actually occurs in vivo, and it is more probable that the glycosylase will prevent processing of the opposite strand by strongly binding to the AP site until the next step in the excision pathway.
[]
Our results suggest that in the case of ROS1 it is unlikely that this circumstance actually occurs in vivo, and it is more probable that the glycosylase will prevent processing of the opposite strand by strongly binding to the AP site until the next step in the excision pathway.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
There are precedents for such protection lingering with its product in other DNA glycosylases.
[ "13", "48", "49" ]
94
40,573
0
false
There are precedents for such protection lingering with its product in other DNA glycosylases.
[]
There are precedents for such protection lingering with its product in other DNA glycosylases.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
Thus, E. coli MutY removes A from 8-oxoG:A mispairs, but remains bound to its product in order to prevent double-strand breaks due to premature 8-oxoG excision by Fpg (48,49).
[ "13", "48", "49" ]
175
40,574
0
false
Thus, E. coli MutY removes A from 8-oxoG:A mispairs, but remains bound to its product in order to prevent double-strand breaks due to premature 8-oxoG excision by Fpg.
[ "48,49" ]
Thus, E. coli MutY removes A from 8-oxoG:A mispairs, but remains bound to its product in order to prevent double-strand breaks due to premature 8-oxoG excision by Fpg.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
The binding of ROS1 to the AP:G intermediate probably also explains the slower 5-meC excision rate observed on bimethylated DNA compared with hemimethylated DNA.
[ "13", "48", "49" ]
161
40,575
0
false
The binding of ROS1 to the AP:G intermediate probably also explains the slower 5-meC excision rate observed on bimethylated DNA compared with hemimethylated DNA.
[]
The binding of ROS1 to the AP:G intermediate probably also explains the slower 5-meC excision rate observed on bimethylated DNA compared with hemimethylated DNA.
true
true
true
true
true
6,999
6
DISCUSSION
1
13
[ "B13", "B48", "B49" ]
19,443,451
pmid-16469697|pmid-1445834|pmid-9778350
It is predicted that product inhibition will be faster in the first case, since the 5-meC/enzyme ratio is 2-fold higher in bimethylated DNA compared to the hemimethylated substrate.
[ "13", "48", "49" ]
181
40,576
0
false
It is predicted that product inhibition will be faster in the first case, since the 5-meC/enzyme ratio is 2-fold higher in bimethylated DNA compared to the hemimethylated substrate.
[]
It is predicted that product inhibition will be faster in the first case, since the 5-meC/enzyme ratio is 2-fold higher in bimethylated DNA compared to the hemimethylated substrate.
true
true
true
true
true
6,999
7
DISCUSSION
0
null
null
19,443,451
null
The action of ROS1 on symmetrical CG sites is further complicated by the fact that the enzyme certainly encounters different sequence contexts in the two strands.
null
162
40,577
0
false
null
null
The action of ROS1 on symmetrical CG sites is further complicated by the fact that the enzyme certainly encounters different sequence contexts in the two strands.
true
true
true
true
true
7,000
7
DISCUSSION
0
null
null
19,443,451
null
We found that 5-meC processing by ROS1 occurs at different rates on each strand of the same DNA molecule.
null
105
40,578
0
false
null
null
We found that 5-meC processing by ROS1 occurs at different rates on each strand of the same DNA molecule.
true
true
true
true
true
7,000
7
DISCUSSION
0
null
null
19,443,451
null
This confounding factor should be taken into account when examining the substrate activity of 5-meC DNA glycosylases on bimethylated substrates.
null
144
40,579
0
false
null
null
This confounding factor should be taken into account when examining the substrate activity of 5-meC DNA glycosylases on bimethylated substrates.
true
true
true
true
true
7,000
8
DISCUSSION
1
45
[ "B45" ]
19,443,451
pmid-15939442
DNA glycosylase processivity has been defined as the ability to excise several close target bases without dissociating from DNA (45).
[ "45" ]
133
40,580
1
false
DNA glycosylase processivity has been defined as the ability to excise several close target bases without dissociating from DNA.
[ "45" ]
DNA glycosylase processivity has been defined as the ability to excise several close target bases without dissociating from DNA.
true
true
true
true
true
7,001
8
DISCUSSION
1
45
[ "B45" ]
19,443,451
pmid-15939442
We tested the processivity of 5-meC excision by ROS1 using a DNA duplex with three target residues separated from each other by 9 nt.
[ "45" ]
133
40,581
0
false
We tested the processivity of 5-meC excision by ROS1 using a DNA duplex with three target residues separated from each other by 9 nt.
[]
We tested the processivity of 5-meC excision by ROS1 using a DNA duplex with three target residues separated from each other by 9 nt.
true
true
true
true
true
7,001
8
DISCUSSION
1
45
[ "B45" ]
19,443,451
pmid-15939442
We found that, under conditions where E. coli Ung displays processive behaviour, ROS1 excises 5-meC in a near-exclusively distributive fashion.
[ "45" ]
143
40,582
0
false
We found that, under conditions where E. coli Ung displays processive behaviour, ROS1 excises 5-meC in a near-exclusively distributive fashion.
[]
We found that, under conditions where E. coli Ung displays processive behaviour, ROS1 excises 5-meC in a near-exclusively distributive fashion.
true
true
true
true
true
7,001
8
DISCUSSION
1
45
[ "B45" ]
19,443,451
pmid-15939442
Our experiments were performed at low salt concentrations (2.5 mM), using DNA substrates that contained target bases in close proximity (9 nt), therefore requiring very little translocation or short range hopping.
[ "45" ]
213
40,583
0
false
Our experiments were performed at low salt concentrations (2.5 mM), using DNA substrates that contained target bases in close proximity (9 nt), therefore requiring very little translocation or short range hopping.
[]
Our experiments were performed at low salt concentrations, using DNA substrates that contained target bases in close proximity (9 nt), therefore requiring very little translocation or short range hopping.
true
true
true
true
true
7,001
8
DISCUSSION
1
45
[ "B45" ]
19,443,451
pmid-15939442
Even under these favourable conditions, no evidence for significant ROS1 processivity was found.
[ "45" ]
96
40,584
0
false
Even under these favourable conditions, no evidence for significant ROS1 processivity was found.
[]
Even under these favourable conditions, no evidence for significant ROS1 processivity was found.
true
true
true
true
true
7,001
9
DISCUSSION
1
50
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
Nevertheless, it should be emphasized that these results do not rule out the possibility that target search by ROS1 proceeds though one-dimensional diffusion by sliding and/or hopping (50).
[ "50", "45", "45", "51", "52", "53", "54" ]
189
40,585
1
false
Nevertheless, it should be emphasized that these results do not rule out the possibility that target search by ROS1 proceeds though one-dimensional diffusion by sliding and/or hopping.
[ "50" ]
Nevertheless, it should be emphasized that these results do not rule out the possibility that target search by ROS1 proceeds though one-dimensional diffusion by sliding and/or hopping.
true
true
true
true
true
7,002
9
DISCUSSION
1
50
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
Processivity is a property arising from correlated cleavage, i.e.
[ "50", "45", "45", "51", "52", "53", "54" ]
65
40,586
0
false
Processivity is a property arising from correlated cleavage, i.e.
[]
Processivity is a property arising from correlated cleavage, i.e.
true
true
true
true
true
7,002
9
DISCUSSION
1
45
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
the probability of the enzyme resuming the walk after catalysis is complete (45).
[ "50", "45", "45", "51", "52", "53", "54" ]
81
40,587
1
false
the probability of the enzyme resuming the walk after catalysis is complete.
[ "45" ]
the probability of the enzyme resuming the walk after catalysis is complete.
false
true
true
true
false
7,002
9
DISCUSSION
1
50
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
In contrast, one-dimensional diffusion applies to correlated searches, i.e.
[ "50", "45", "45", "51", "52", "53", "54" ]
75
40,588
0
false
In contrast, one-dimensional diffusion applies to correlated searches, i.e.
[]
In contrast, one-dimensional diffusion applies to correlated searches, i.e.
true
true
true
true
true
7,002
9
DISCUSSION
1
45
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
the probability that the enzyme remains bound to the DNA after one step of random walk (45).
[ "50", "45", "45", "51", "52", "53", "54" ]
92
40,589
1
false
the probability that the enzyme remains bound to the DNA after one step of random walk.
[ "45" ]
the probability that the enzyme remains bound to the DNA after one step of random walk.
false
true
true
true
false
7,002
9
DISCUSSION
1
53
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
A case in point is hOGG1, which at physiological salt concentrations displays limited processivity (51,52) but undergoes rapid sliding while searching for target lesions (53).
[ "50", "45", "45", "51", "52", "53", "54" ]
175
40,590
1
false
A case in point is hOGG1, which at physiological salt concentrations displays limited processivity but undergoes rapid sliding while searching for target lesions.
[ "51,52", "53" ]
A case in point is hOGG1, which at physiological salt concentrations displays limited processivity but undergoes rapid sliding while searching for target lesions.
true
true
true
true
true
7,002
9
DISCUSSION
1
54
[ "B50", "B45", "B45", "B51", "B52", "B53", "B54" ]
19,443,451
pmid-12848584|pmid-15939442|pmid-15939442|pmid-17126083|pmid-18672903|pmid-16585517|pmid-9867812
In this regard it should be noted that ROS1 displays some non-specific DNA binding, a property also found in other DNA glycosylases such as TDG (54).
[ "50", "45", "45", "51", "52", "53", "54" ]
149
40,591
1
false
In this regard it should be noted that ROS1 displays some non-specific DNA binding, a property also found in other DNA glycosylases such as TDG.
[ "54" ]
In this regard it should be noted that ROS1 displays some non-specific DNA binding, a property also found in other DNA glycosylases such as TDG.
true
true
true
true
true
7,002
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
The very low processivity of ROS1 is remarkable, even by comparison with enzymes that are catalytically less efficient than Ung.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
128
40,592
0
false
The very low processivity of ROS1 is remarkable, even by comparison with enzymes that are catalytically less efficient than Ung.
[]
The very low processivity of ROS1 is remarkable, even by comparison with enzymes that are catalytically less efficient than Ung.
true
true
true
true
true
7,003
10
DISCUSSION
1
60
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
In addition to Ung (55,56), other DNA glycosylases such as hOGG1, Fpg, MutY, T4-pdg and human alkyladenine DNA glycosylase (AAG) (52,57–59) as well as human AP endonuclease (APE1) (60), exhibit some degree of significant processivity when tested at low salt concentration.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
272
40,593
1
false
In addition to Ung, other DNA glycosylases such as hOGG1, Fpg, MutY, T4-pdg and human alkyladenine DNA glycosylase (AAG) as well as human AP endonuclease (APE1), exhibit some degree of significant processivity when tested at low salt concentration.
[ "55,56", "52,57–59", "60" ]
In addition to Ung, other DNA glycosylases such as hOGG1, Fpg, MutY, T4-pdg and human alkyladenine DNA glycosylase (AAG) as well as human AP endonuclease (APE1), exhibit some degree of significant processivity when tested at low salt concentration.
true
true
true
true
true
7,003
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
A distributive initiation of demethylation events may be well suited for an enzyme possibly performing a protecting role in a plant genome containing significant amounts of 5-meC.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
179
40,594
0
false
A distributive initiation of demethylation events may be well suited for an enzyme possibly performing a protecting role in a plant genome containing significant amounts of 5-meC.
[]
A distributive initiation of demethylation events may be well suited for an enzyme possibly performing a protecting role in a plant genome containing significant amounts of 5-meC.
true
true
true
true
true
7,003
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
Genome-wide methylation analyses have uncovered hundreds of discrete hypermethylated regions in ros1 dml2 dml3 triple-mutant plants, but overall DNA methylation levels are similar to those of wild-type plants (20,23).
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
217
40,595
0
false
Genome-wide methylation analyses have uncovered hundreds of discrete hypermethylated regions in ros1 dml2 dml3 triple-mutant plants, but overall DNA methylation levels are similar to those of wild-type plants.
[ "20,23" ]
Genome-wide methylation analyses have uncovered hundreds of discrete hypermethylated regions in ros1 dml2 dml3 triple-mutant plants, but overall DNA methylation levels are similar to those of wild-type plants.
true
true
true
true
true
7,003
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
Hypermethylation primarily affects the 5β€² and 3β€² gene ends in genic regions (20,23), but also transposon sequences (22,23).
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
123
40,596
0
false
Hypermethylation primarily affects the 5β€² and 3β€² gene ends in genic regions, but also transposon sequences.
[ "20,23", "22,23" ]
Hypermethylation primarily affects the 5β€² and 3β€² gene ends in genic regions, but also transposon sequences.
true
true
true
true
true
7,003
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
Therefore, 5-meC DNA glycosylases seem to be active throughout the genome at a variety of loci.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
95
40,597
0
false
Therefore, 5-meC DNA glycosylases seem to be active throughout the genome at a variety of loci.
[]
Therefore, 5-meC DNA glycosylases seem to be active throughout the genome at a variety of loci.
true
true
true
true
true
7,003
10
DISCUSSION
1
61
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
There is strong evidence suggesting that demethylation by ROS1 may be guided by small RNAs bound to ROS3 (61), but it is still an open question whether ROS1 and related enzymes are targeted to specific DNA sequences for unknown reasons or simply to genomic regions that are likely to suffer excessive methylation.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
313
40,598
1
false
There is strong evidence suggesting that demethylation by ROS1 may be guided by small RNAs bound to ROS3, but it is still an open question whether ROS1 and related enzymes are targeted to specific DNA sequences for unknown reasons or simply to genomic regions that are likely to suffer excessive methylation.
[ "61" ]
There is strong evidence suggesting that demethylation by ROS1 may be guided by small RNAs bound to ROS3, but it is still an open question whether ROS1 and related enzymes are targeted to specific DNA sequences for unknown reasons or simply to genomic regions that are likely to suffer excessive methylation.
true
true
true
true
true
7,003
10
DISCUSSION
1
61
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
The ROS3-dependent demethylation of a transgenic locus subjected to continuous short interfering RNA (siRNA)-directed DNA methylation (61) seems to argue in favor of the latter possibility.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
189
40,599
1
false
The ROS3-dependent demethylation of a transgenic locus subjected to continuous short interfering RNA (siRNA)-directed DNA methylation seems to argue in favor of the latter possibility.
[ "61" ]
The ROS3-dependent demethylation of a transgenic locus subjected to continuous short interfering RNA (siRNA)-directed DNA methylation seems to argue in favor of the latter possibility.
true
true
true
true
true
7,003
10
DISCUSSION
1
20
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
Overall, the available data suggest that one of the functions of plant 5-meC DNA glycosylases is to counteract excess DNA methylation, thus protecting the plant genome from a robust DNA modification machinery that evolved for defensive purposes (20).
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
250
40,600
1
false
Overall, the available data suggest that one of the functions of plant 5-meC DNA glycosylases is to counteract excess DNA methylation, thus protecting the plant genome from a robust DNA modification machinery that evolved for defensive purposes.
[ "20" ]
Overall, the available data suggest that one of the functions of plant 5-meC DNA glycosylases is to counteract excess DNA methylation, thus protecting the plant genome from a robust DNA modification machinery that evolved for defensive purposes.
true
true
true
true
true
7,003
10
DISCUSSION
1
55
[ "B55", "B56", "B52", "B57 B58 B59", "B60", "B20", "B23", "B20", "B23", "B22", "B23", "B61", "B61", "B20" ]
19,443,451
pmid-18201572|pmid-7742315|pmid-18672903|pmid-12534293|pmid-18839966|pmid-15923014|pmid-10600117|pmid-17409185|pmid-18423832|pmid-17409185|pmid-18423832|pmid-17208187|pmid-18423832|pmid-18815596|pmid-18815596|pmid-17409185
This idea is consistent with the hypothesis that plant 5-meC DNA glycosylases diverged from a common ancestor dedicated to DNA maintenance.
[ "55", "56", "52", "57–59", "60", "20", "23", "20", "23", "22", "23", "61", "61", "20" ]
139
40,601
0
false
This idea is consistent with the hypothesis that plant 5-meC DNA glycosylases diverged from a common ancestor dedicated to DNA maintenance.
[]
This idea is consistent with the hypothesis that plant 5-meC DNA glycosylases diverged from a common ancestor dedicated to DNA maintenance.
true
true
true
true
true
7,003
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5", "B6", "B7" ]
18,385,154
pmid-16807135|pmid-11242102|pmid-12186839|pmid-12846809|pmid-12947387|pmid-15189136|pmid-8700231|pmid-12697833|pmid-9545646|pmid-16397222
DNA double-strand breaks (DSBs) can be caused by both cell-intrinsic sources, such as replication errors or reactive oxygen species, and a variety of extrinsic factors, including ionizing radiation (IR) and radiomimetic chemicals.
[ "1–5", "6", "7" ]
230
40,602
0
false
DNA double-strand breaks (DSBs) can be caused by both cell-intrinsic sources, such as replication errors or reactive oxygen species, and a variety of extrinsic factors, including ionizing radiation (IR) and radiomimetic chemicals.
[]
DNA double-strand breaks (DSBs) can be caused by both cell-intrinsic sources, such as replication errors or reactive oxygen species, and a variety of extrinsic factors, including ionizing radiation (IR) and radiomimetic chemicals.
true
true
true
true
true
7,004
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5", "B6", "B7" ]
18,385,154
pmid-16807135|pmid-11242102|pmid-12186839|pmid-12846809|pmid-12947387|pmid-15189136|pmid-8700231|pmid-12697833|pmid-9545646|pmid-16397222
DSBs representing the most toxic DNA lesions, if left unrepaired, may cause cell death and genomic instability.
[ "1–5", "6", "7" ]
111
40,603
0
false
DSBs representing the most toxic DNA lesions, if left unrepaired, may cause cell death and genomic instability.
[]
DSBs representing the most toxic DNA lesions, if left unrepaired, may cause cell death and genomic instability.
true
true
true
true
true
7,004
0
INTRODUCTION
1
1–5
[ "B1 B2 B3 B4 B5", "B6", "B7" ]
18,385,154
pmid-16807135|pmid-11242102|pmid-12186839|pmid-12846809|pmid-12947387|pmid-15189136|pmid-8700231|pmid-12697833|pmid-9545646|pmid-16397222
Inefficient or inaccurate repair may lead to mutation and/or chromosome rearrangement, and predisposition to cancer (1–5).
[ "1–5", "6", "7" ]
122
40,604
1
false
Inefficient or inaccurate repair may lead to mutation and/or chromosome rearrangement, and predisposition to cancer.
[ "1–5" ]
Inefficient or inaccurate repair may lead to mutation and/or chromosome rearrangement, and predisposition to cancer.
true
true
true
true
true
7,004
0
INTRODUCTION
1
6
[ "B1 B2 B3 B4 B5", "B6", "B7" ]
18,385,154
pmid-16807135|pmid-11242102|pmid-12186839|pmid-12846809|pmid-12947387|pmid-15189136|pmid-8700231|pmid-12697833|pmid-9545646|pmid-16397222
DSBs also represent obligatory intermediates of physiological DNA rearrangement processes taking place during the development and maturation of the adaptive immune system, V(D)J recombination and immunoglobulin (Ig) heavy-chain class switch recombination (CSR) (6).
[ "1–5", "6", "7" ]
265
40,605
1
false
DSBs also represent obligatory intermediates of physiological DNA rearrangement processes taking place during the development and maturation of the adaptive immune system, V(D)J recombination and immunoglobulin (Ig) heavy-chain class switch recombination (CSR).
[ "6" ]
DSBs also represent obligatory intermediates of physiological DNA rearrangement processes taking place during the development and maturation of the adaptive immune system, V(D)J recombination and immunoglobulin (Ig) heavy-chain class switch recombination (CSR).
true
true
true
true
true
7,004
0
INTRODUCTION
1
7
[ "B1 B2 B3 B4 B5", "B6", "B7" ]
18,385,154
pmid-16807135|pmid-11242102|pmid-12186839|pmid-12846809|pmid-12947387|pmid-15189136|pmid-8700231|pmid-12697833|pmid-9545646|pmid-16397222
Therefore, defects in the repair of these DNA breaks can cause profound immuno-deficiencies (7).
[ "1–5", "6", "7" ]
96
40,606
1
false
Therefore, defects in the repair of these DNA breaks can cause profound immuno-deficiencies.
[ "7" ]
Therefore, defects in the repair of these DNA breaks can cause profound immuno-deficiencies.
true
true
true
true
true
7,004
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Eukaryotes cells have evolved two major pathways for repairing DSBs, homologous recombination (HR) and nonhomologous end joining (NHEJ).
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
136
40,607
0
false
Eukaryotes cells have evolved two major pathways for repairing DSBs, homologous recombination (HR) and nonhomologous end joining (NHEJ).
[]
Eukaryotes cells have evolved two major pathways for repairing DSBs, homologous recombination (HR) and nonhomologous end joining (NHEJ).
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Both pathways are conserved from yeast to mammals and function in complementary ways to repair DSBs (1,5,8).
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
108
40,608
0
false
Both pathways are conserved from yeast to mammals and function in complementary ways to repair DSBs.
[ "1,5,8" ]
Both pathways are conserved from yeast to mammals and function in complementary ways to repair DSBs.
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
During HR, DSBs are repaired through a precise pathway that uses homologous sequence usually provided by the sister chromatid during replication as for template.
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
161
40,609
0
false
During HR, DSBs are repaired through a precise pathway that uses homologous sequence usually provided by the sister chromatid during replication as for template.
[]
During HR, DSBs are repaired through a precise pathway that uses homologous sequence usually provided by the sister chromatid during replication as for template.
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
In contrast, NHEJ is an error-prone repair pathway that joins ends together without the requirement for significant sequence homology (1,5,8).
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
142
40,610
0
false
In contrast, NHEJ is an error-prone repair pathway that joins ends together without the requirement for significant sequence homology.
[ "1,5,8" ]
In contrast, NHEJ is an error-prone repair pathway that joins ends together without the requirement for significant sequence homology.
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Once DSBs are produced, cells trigger a series of signaling pathway including cycle regulation, transcription, histone modification and apoptosis that have direct or indirect effect on DSB repair.
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
196
40,611
0
false
Once DSBs are produced, cells trigger a series of signaling pathway including cycle regulation, transcription, histone modification and apoptosis that have direct or indirect effect on DSB repair.
[]
Once DSBs are produced, cells trigger a series of signaling pathway including cycle regulation, transcription, histone modification and apoptosis that have direct or indirect effect on DSB repair.
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Following DNA damage, the DNA damage sensors ATM/ATR and DNA-PK phosphorylate CHK1 and CHK2 to regulate cell cycle checkpoint, phosphorylate P53 to activate apoptosis signal pathway, phosphorylate H2AX and a number of proteins involved in DSB repair such as NBS1 and SMC1 (5,9).
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
278
40,612
0
false
Following DNA damage, the DNA damage sensors ATM/ATR and DNA-PK phosphorylate CHK1 and CHK2 to regulate cell cycle checkpoint, phosphorylate P53 to activate apoptosis signal pathway, phosphorylate H2AX and a number of proteins involved in DSB repair such as NBS1 and SMC1.
[ "5,9" ]
Following DNA damage, the DNA damage sensors ATM/ATR and DNA-PK phosphorylate CHK1 and CHK2 to regulate cell cycle checkpoint, phosphorylate P53 to activate apoptosis signal pathway, phosphorylate H2AX and a number of proteins involved in DSB repair such as NBS1 and SMC1.
true
true
true
true
true
7,005
1
INTRODUCTION
1
10
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Besides phosphorylation of H2AX, recently, histone ubiquitinations, acetylations and methylations have been implicated in the DNA damage checkpoint and DSBs repair pathways (10).
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
178
40,613
1
false
Besides phosphorylation of H2AX, recently, histone ubiquitinations, acetylations and methylations have been implicated in the DNA damage checkpoint and DSBs repair pathways.
[ "10" ]
Besides phosphorylation of H2AX, recently, histone ubiquitinations, acetylations and methylations have been implicated in the DNA damage checkpoint and DSBs repair pathways.
true
true
true
true
true
7,005
1
INTRODUCTION
1
1
[ "B1", "B5", "B8", "B1", "B5", "B8", "B5", "B9", "B10" ]
18,385,154
pmid-16807135|pmid-12947387|pmid-15175261|pmid-16807135|pmid-12947387|pmid-15175261|pmid-12947387|pmid-12612651|pmid-15989948
Although the last few years a wealth of new information has been produced about DSBs damage response and DNA repair, and many novel proteins involved in the process have been identified, the process still remains elusive.
[ "1", "5", "8", "1", "5", "8", "5", "9", "10" ]
221
40,614
0
false
Although the last few years a wealth of new information has been produced about DSBs damage response and DNA repair, and many novel proteins involved in the process have been identified, the process still remains elusive.
[]
Although the last few years a wealth of new information has been produced about DSBs damage response and DNA repair, and many novel proteins involved in the process have been identified, the process still remains elusive.
true
true
true
true
true
7,005
2
INTRODUCTION
1
11–13
[ "B11 B12 B13", "B14", "B15", "B15 B16 B17 B18", "B19", "B20" ]
18,385,154
pmid-15365186|pmid-16141234|pmid-17439963|pmid-12628181|pmid-15315754|pmid-15315754|pmid-17060944|pmid-17374722|pmid-17560333|pmid-16855786|pmid-16452150|pmid-15525939|pmid-16728978|pmid-16728976|pmid-16728974|pmid-16728977
With the aim of identifying new factors involved in DSBs damage response and repair of mammalian cells, we screened a number of proteins involved in chromatin remodeling and regulation by using laser micro-irradiation system (11–13).
[ "11–13", "14", "15", "15–18", "19", "20" ]
233
40,615
1
false
With the aim of identifying new factors involved in DSBs damage response and repair of mammalian cells, we screened a number of proteins involved in chromatin remodeling and regulation by using laser micro-irradiation system.
[ "11–13" ]
With the aim of identifying new factors involved in DSBs damage response and repair of mammalian cells, we screened a number of proteins involved in chromatin remodeling and regulation by using laser micro-irradiation system.
true
true
true
true
true
7,006