Datasets:
vgainullin
/
xciting_data

Dataset card Data Studio Files
xet
 Community
1
paragraph_index
int64
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string
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int64
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int64
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4
DISCUSSION
1
26
[ "B26" ]
17,289,752
pmid-10600105
Notably, when either EcoNth or EcoFpg was trapped with the 5R substrate, a lower accessibility parameter, Φ, was apparent.
[ "26" ]
122
6,100
0
false
Notably, when either EcoNth or EcoFpg was trapped with the 5R substrate, a lower accessibility parameter, Φ, was apparent.
[]
Notably, when either EcoNth or EcoFpg was trapped with the 5R substrate, a lower accessibility parameter, Φ, was apparent.
true
true
true
true
true
1,010
4
DISCUSSION
1
26
[ "B26" ]
17,289,752
pmid-10600105
In each case, particularly with EcoFpg, the only predicted binding mode of DAPI with a greater than 3 Å distance from the enzyme is the ATTG-binding mode.
[ "26" ]
154
6,101
0
false
In each case, particularly with EcoFpg, the only predicted binding mode of DAPI with a greater than 3 Å distance from the enzyme is the ATTG-binding mode.
[]
In each case, particularly with EcoFpg, the only predicted binding mode of DAPI with a greater than 3 Å distance from the enzyme is the ATTG-binding mode.
true
true
true
true
true
1,010
4
DISCUSSION
1
26
[ "B26" ]
17,289,752
pmid-10600105
When this structure was published, the authors were unable to unequivocally state that this AT/GC binding mode was sequence specific and not simply an artifact of crystal packing (26).
[ "26" ]
184
6,102
1
false
When this structure was published, the authors were unable to unequivocally state that this AT/GC binding mode was sequence specific and not simply an artifact of crystal packing.
[ "26" ]
When this structure was published, the authors were unable to unequivocally state that this AT/GC binding mode was sequence specific and not simply an artifact of crystal packing.
true
true
true
true
true
1,010
4
DISCUSSION
1
26
[ "B26" ]
17,289,752
pmid-10600105
The data presented here provide further evidence of alternative DAPI-binding modes, and does not rule out the possibility of the AT/GC association.
[ "26" ]
147
6,103
0
false
The data presented here provide further evidence of alternative DAPI-binding modes, and does not rule out the possibility of the AT/GC association.
[]
The data presented here provide further evidence of alternative DAPI-binding modes, and does not rule out the possibility of the AT/GC association.
true
true
true
true
true
1,010
4
DISCUSSION
1
26
[ "B26" ]
17,289,752
pmid-10600105
No claims can be made, however, on the preference of one binding site over another.
[ "26" ]
83
6,104
0
false
No claims can be made, however, on the preference of one binding site over another.
[]
No claims can be made, however, on the preference of one binding site over another.
true
true
true
true
true
1,010
5
DISCUSSION
0
null
null
17,289,752
null
As mentioned above, drug association may be modulated by either steric hindrance from the enzyme at the predicted DAPI-binding site and/or protection of the DAPI-binding site by orientation of the minor groove in relation to the protein.
null
237
6,105
0
false
null
null
As mentioned above, drug association may be modulated by either steric hindrance from the enzyme at the predicted DAPI-binding site and/or protection of the DAPI-binding site by orientation of the minor groove in relation to the protein.
true
true
true
true
true
1,011
5
DISCUSSION
0
null
null
17,289,752
null
The fact that EcoFpg and the 4L substrate can accurately determine the active enzyme fraction (Figure 4B and D), and that both predicted binding modes for the EcoFpg–4L trapped complex have at least one orientation of DAPI which is not sterically hindered (Table 1), suggests that orientation of the DAPI-binding site is...
null
378
6,106
0
false
null
null
The fact that EcoFpg and the 4L substrate can accurately determine the active enzyme fraction (Figure 4B and D), and that both predicted binding modes for the EcoFpg–4L trapped complex have at least one orientation of DAPI which is not sterically hindered (Table 1), suggests that orientation of the DAPI-binding site is...
true
true
true
true
true
1,011
5
DISCUSSION
0
null
null
17,289,752
null
It should be noted that although the 5L substrate is generally classified as ‘internally facing’, one orientation of DAPI in the ATTG binding mode with trapped EcoFpg is externally facing due to the distance of DAPI from the enzyme.
null
232
6,107
0
false
null
null
It should be noted that although the 5L substrate is generally classified as ‘internally facing’, one orientation of DAPI in the ATTG binding mode with trapped EcoFpg is externally facing due to the distance of DAPI from the enzyme.
true
true
true
true
true
1,011
5
DISCUSSION
0
null
null
17,289,752
null
It is presumably for this reason that the 5L substrate is unable to accurately determine the active fraction with EcoFpg, since the other predicted binding configurations have internally facing DAPI-binding sites.
null
213
6,108
0
false
null
null
It is presumably for this reason that the 5L substrate is unable to accurately determine the active fraction with EcoFpg, since the other predicted binding configurations have internally facing DAPI-binding sites.
true
true
true
true
true
1,011
6
DISCUSSION
0
null
null
17,289,752
null
In this study, we have demonstrated a rapid, fluorescence-based approach for determining the number of bound versus unbound BER enzymes to damaged oligonucleotides following Schiff base trapping.
null
195
6,109
0
false
null
null
In this study, we have demonstrated a rapid, fluorescence-based approach for determining the number of bound versus unbound BER enzymes to damaged oligonucleotides following Schiff base trapping.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
The use of the 4L sequence context correctly determines enzyme activity from relative fluorescence calculations (no calibration necessary), for numerous DNA glycosylases from multiple phylogenetic families.
null
206
6,110
0
false
null
null
The use of the 4L sequence context correctly determines enzyme activity from relative fluorescence calculations (no calibration necessary), for numerous DNA glycosylases from multiple phylogenetic families.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
The total experimental time is reduced from the standard 1–2 days using a traditional gel-based method, to under 1 h for the DAPI-based method.
null
143
6,111
0
false
null
null
The total experimental time is reduced from the standard 1–2 days using a traditional gel-based method, to under 1 h for the DAPI-based method.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
In a 96-well microplate format, the number of concurrent samples which can be tested also scales well.
null
102
6,112
0
false
null
null
In a 96-well microplate format, the number of concurrent samples which can be tested also scales well.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
Additionally, neither radioactive nor fluorescent labels are required for substrate DNA.
null
88
6,113
0
false
null
null
Additionally, neither radioactive nor fluorescent labels are required for substrate DNA.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
These benefits have allowed us to undertake frequent activity monitoring of enzyme stocks in our laboratory.
null
108
6,114
0
false
null
null
These benefits have allowed us to undertake frequent activity monitoring of enzyme stocks in our laboratory.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
One enzyme in particular has been found to drop from over 80% activity to 20% within a matter of weeks after initial purification.
null
130
6,115
0
false
null
null
One enzyme in particular has been found to drop from over 80% activity to 20% within a matter of weeks after initial purification.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
The testing of numerous optimized storage conditions can now be accomplished in minimal time.
null
93
6,116
0
false
null
null
The testing of numerous optimized storage conditions can now be accomplished in minimal time.
true
true
true
true
true
1,012
6
DISCUSSION
0
null
null
17,289,752
null
In conclusion, the molecular accessibility assay, specifically in conjunction with DAPI and the 4L substrate, should be useful in the study of numerous DNA-binding proteins.
null
173
6,117
0
false
null
null
In conclusion, the molecular accessibility assay, specifically in conjunction with DAPI and the 4L substrate, should be useful in the study of numerous DNA-binding proteins.
true
true
true
true
true
1,012
0
INTRODUCTION
1
1–3
[ "B1 B2 B3", "B4", "B5" ]
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Uracil is a common base lesion in DNA and is introduced into the genome by deamination of cytosine and misincorporation of dUMP instead of dTMP during replication.
[ "1–3", "4", "5" ]
163
6,118
0
false
Uracil is a common base lesion in DNA and is introduced into the genome by deamination of cytosine and misincorporation of dUMP instead of dTMP during replication.
[]
Uracil is a common base lesion in DNA and is introduced into the genome by deamination of cytosine and misincorporation of dUMP instead of dTMP during replication.
true
true
true
true
true
1,013
0
INTRODUCTION
1
1–3
[ "B1 B2 B3", "B4", "B5" ]
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Spontaneous deamination of cytosine has been estimated to occur at a rate of 60–500 events per day in human cells (1–3).
[ "1–3", "4", "5" ]
120
6,119
1
false
Spontaneous deamination of cytosine has been estimated to occur at a rate of 60–500 events per day in human cells.
[ "1–3" ]
Spontaneous deamination of cytosine has been estimated to occur at a rate of 60–500 events per day in human cells.
true
true
true
true
true
1,013
0
INTRODUCTION
1
4
[ "B1 B2 B3", "B4", "B5" ]
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
In addition, recent research has revealed that enzymatic deamination of cytosine at the Ig loci by activation-induced cytosine deaminase (AID) initiates the antigen-dependent antibody diversification processes (4).
[ "1–3", "4", "5" ]
214
6,120
1
false
In addition, recent research has revealed that enzymatic deamination of cytosine at the Ig loci by activation-induced cytosine deaminase (AID) initiates the antigen-dependent antibody diversification processes.
[ "4" ]
In addition, recent research has revealed that enzymatic deamination of cytosine at the Ig loci by activation-induced cytosine deaminase (AID) initiates the antigen-dependent antibody diversification processes.
true
true
true
true
true
1,013
0
INTRODUCTION
1
1–3
[ "B1 B2 B3", "B4", "B5" ]
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Uracil generated by deamination of cytosine is 100% miscoding, and result in C:G to T:A transition mutations if not repaired prior to replication.
[ "1–3", "4", "5" ]
146
6,121
0
false
Uracil generated by deamination of cytosine is 100% miscoding, and result in C:G to T:A transition mutations if not repaired prior to replication.
[]
Uracil generated by deamination of cytosine is 100% miscoding, and result in C:G to T:A transition mutations if not repaired prior to replication.
true
true
true
true
true
1,013
0
INTRODUCTION
1
5
[ "B1 B2 B3", "B4", "B5" ]
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Misincorporated uracil is not directly miscoding, but it appears to be a critical source of spontaneously generated AP-sites (apurinic/apyrimidinic-sites) in the genome (5).
[ "1–3", "4", "5" ]
173
6,122
1
false
Misincorporated uracil is not directly miscoding, but it appears to be a critical source of spontaneously generated AP-sites (apurinic/apyrimidinic-sites) in the genome.
[ "5" ]
Misincorporated uracil is not directly miscoding, but it appears to be a critical source of spontaneously generated AP-sites (apurinic/apyrimidinic-sites) in the genome.
true
true
true
true
true
1,013
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Uracil and some uracil analogs generated by oxidation of cytosine are excised from the genome by uracil-DNA glycosylases (UDGs).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
128
6,123
0
false
Uracil and some uracil analogs generated by oxidation of cytosine are excised from the genome by uracil-DNA glycosylases (UDGs).
[]
Uracil and some uracil analogs generated by oxidation of cytosine are excised from the genome by uracil-DNA glycosylases (UDGs).
true
true
true
true
true
1,014
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Mammalian cell nuclei contain at least four UDGs; UNG2, SMUG1, TDG and MBD4.
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
76
6,124
0
false
Mammalian cell nuclei contain at least four UDGs; UNG2, SMUG1, TDG and MBD4.
[]
Mammalian cell nuclei contain at least four UDGs; UNG2, SMUG1, TDG and MBD4.
true
true
true
true
true
1,014
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Current evidence suggests that UNG2 (uracil-N-glycosylase 2) and SMUG1 (single-strand-selective monofunctional UDG) are the major enzymes responsible for repair of spontaneously deaminated cytosine (6–8), while post-replicative excision of misincorporated dUMP (U:A) and excision of AID-generated uracil (U:G) are perfor...
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
352
6,125
1
false
Current evidence suggests that UNG2 (uracil-N-glycosylase 2) and SMUG1 (single-strand-selective monofunctional UDG) are the major enzymes responsible for repair of spontaneously deaminated cytosine, while post-replicative excision of misincorporated dUMP (U:A) and excision of AID-generated uracil (U:G) are performed ma...
[ "6–8", "9–11" ]
Current evidence suggests that UNG2 (uracil-N-glycosylase 2) and SMUG1 (single-strand-selective monofunctional UDG) are the major enzymes responsible for repair of spontaneously deaminated cytosine, while post-replicative excision of misincorporated dUMP (U:A) and excision of AID-generated uracil (U:G) are performed ma...
true
true
true
true
true
1,014
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Consistent with the role of UNG2 in replication associated repair, UNG2 binds PCNA and RPA, is localized to replication foci, and is cell cycle regulated with the highest levels in S-phase (9,12–15).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
199
6,126
0
false
Consistent with the role of UNG2 in replication associated repair, UNG2 binds PCNA and RPA, is localized to replication foci, and is cell cycle regulated with the highest levels in S-phase.
[ "9,12–15" ]
Consistent with the role of UNG2 in replication associated repair, UNG2 binds PCNA and RPA, is localized to replication foci, and is cell cycle regulated with the highest levels in S-phase.
true
true
true
true
true
1,014
1
INTRODUCTION
1
7
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Conversely, SMUG1, is not cell cycle regulated and is evenly distributed in the nucleoplasm (7).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
96
6,127
1
false
Conversely, SMUG1, is not cell cycle regulated and is evenly distributed in the nucleoplasm.
[ "7" ]
Conversely, SMUG1, is not cell cycle regulated and is evenly distributed in the nucleoplasm.
true
true
true
true
true
1,014
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
SMUG1 excises uracil from DNA with a much lower efficiency than UNG2, but has broader substrate specificity.
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
108
6,128
0
false
SMUG1 excises uracil from DNA with a much lower efficiency than UNG2, but has broader substrate specificity.
[]
SMUG1 excises uracil from DNA with a much lower efficiency than UNG2, but has broader substrate specificity.
true
true
true
true
true
1,014
1
INTRODUCTION
1
6–8
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Only SMUG1 excises thymine with an oxidized methyl group (7,16).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
64
6,129
0
false
Only SMUG1 excises thymine with an oxidized methyl group.
[ "7,16" ]
Only SMUG1 excises thymine with an oxidized methyl group.
true
true
true
true
true
1,014
1
INTRODUCTION
1
17
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
UNG and SMUG1 belong to a superfamily that has apparently evolved from the same ancestral gene (17).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
100
6,130
1
false
UNG and SMUG1 belong to a superfamily that has apparently evolved from the same ancestral gene.
[ "17" ]
UNG and SMUG1 belong to a superfamily that has apparently evolved from the same ancestral gene.
true
true
true
true
true
1,014
1
INTRODUCTION
1
18
[ "B6 B7 B8", "B9 B10 B11", "B9", "B12 B13 B14 B15", "B7", "B7", "B16", "B17", "B18" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Comparison of crystal structures of human UNG and Xenopus SMUG1 has revealed that these enzymes share a common fold and that the SMUG1 active site is a mosaic of features from UNG and MUG/TDG enzyme families (18).
[ "6–8", "9–11", "9", "12–15", "7", "7", "16", "17", "18" ]
213
6,131
1
false
Comparison of crystal structures of human UNG and Xenopus SMUG1 has revealed that these enzymes share a common fold and that the SMUG1 active site is a mosaic of features from UNG and MUG/TDG enzyme families.
[ "18" ]
Comparison of crystal structures of human UNG and Xenopus SMUG1 has revealed that these enzymes share a common fold and that the SMUG1 active site is a mosaic of features from UNG and MUG/TDG enzyme families.
true
true
true
true
true
1,014
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
UNG is widely distributed in bacteria, eukaryotes and even some large DNA viruses, while SMUG1 has previously been reported to be present in vertebrates and insects only (6,17).
[ "6", "17" ]
177
6,132
0
false
UNG is widely distributed in bacteria, eukaryotes and even some large DNA viruses, while SMUG1 has previously been reported to be present in vertebrates and insects only.
[ "6,17" ]
UNG is widely distributed in bacteria, eukaryotes and even some large DNA viruses, while SMUG1 has previously been reported to be present in vertebrates and insects only.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Here we report the existence of bacteria that contain SMUG1 as their only identified UDG.
[ "6", "17" ]
89
6,133
0
false
Here we report the existence of bacteria that contain SMUG1 as their only identified UDG.
[]
Here we report the existence of bacteria that contain SMUG1 as their only identified UDG.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Interestingly, identification of these bacterial SMUG1 orthologs shed new light on the origin of SMUG1 and UNG.
[ "6", "17" ]
111
6,134
0
false
Interestingly, identification of these bacterial SMUG1 orthologs shed new light on the origin of SMUG1 and UNG.
[]
Interestingly, identification of these bacterial SMUG1 orthologs shed new light on the origin of SMUG1 and UNG.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Vertebrates contain both SMUG1 and UNG, but their distinct roles in base excision repair (BER) of deaminated cytosine are still not fully defined.
[ "6", "17" ]
146
6,135
0
false
Vertebrates contain both SMUG1 and UNG, but their distinct roles in base excision repair (BER) of deaminated cytosine are still not fully defined.
[]
Vertebrates contain both SMUG1 and UNG, but their distinct roles in base excision repair (BER) of deaminated cytosine are still not fully defined.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
We have compared the repair mechanisms of human SMUG1 (hSMUG1) and human UNG2 (hUNG2) on deaminated cytosine, in vivo by using replicating ung− Escherichia coli cells containing AID-induced U:G lesions, and in vitro using purified enzymes (hSMUG1, hUNG2 and hAPE1) including a panel of hSMUG1 mutants.
[ "6", "17" ]
301
6,136
0
false
We have compared the repair mechanisms of human SMUG1 (hSMUG1) and human UNG2 (hUNG2) on deaminated cytosine, in vivo by using replicating ung− Escherichia coli cells containing AID-induced U:G lesions, and in vitro using purified enzymes (hSMUG1, hUNG2 and hAPE1) including a panel of hSMUG1 mutants.
[]
We have compared the repair mechanisms of human SMUG1 (hSMUG1) and human UNG2 (hUNG2) on deaminated cytosine, in vivo by using replicating ung− Escherichia coli cells containing AID-induced U:G lesions, and in vitro using purified enzymes (hSMUG1, hUNG2 and hAPE1) including a panel of hSMUG1 mutants.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
We find that only hUNG2 can complement E. coli Ung in repair of U:G mismatches, whereas hSMUG1 inhibits cell proliferation in the same system.
[ "6", "17" ]
142
6,137
0
false
We find that only hUNG2 can complement E. coli Ung in repair of U:G mismatches, whereas hSMUG1 inhibits cell proliferation in the same system.
[]
We find that only hUNG2 can complement E. coli Ung in repair of U:G mismatches, whereas hSMUG1 inhibits cell proliferation in the same system.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
In vitro analyses reveal that hSMUG1 and hUNG2 coordinate the initial steps of BER by distinct mechanisms.
[ "6", "17" ]
106
6,138
0
false
In vitro analyses reveal that hSMUG1 and hUNG2 coordinate the initial steps of BER by distinct mechanisms.
[]
In vitro analyses reveal that hSMUG1 and hUNG2 coordinate the initial steps of BER by distinct mechanisms.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Furthermore, we characterize a specific motif in hSMUG1 that confers U:G-substrate preference and stabilizes the product AP-site binding.
[ "6", "17" ]
137
6,139
0
false
Furthermore, we characterize a specific motif in hSMUG1 that confers U:G-substrate preference and stabilizes the product AP-site binding.
[]
Furthermore, we characterize a specific motif in hSMUG1 that confers U:G-substrate preference and stabilizes the product AP-site binding.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Finally, we propose a model for how SMUG1 and UNG2 initiate and coordinate repair of deaminated cytosine (U:G) by distinct mechanisms.
[ "6", "17" ]
134
6,140
0
false
Finally, we propose a model for how SMUG1 and UNG2 initiate and coordinate repair of deaminated cytosine (U:G) by distinct mechanisms.
[]
Finally, we propose a model for how SMUG1 and UNG2 initiate and coordinate repair of deaminated cytosine (U:G) by distinct mechanisms.
true
true
true
true
true
1,015
2
INTRODUCTION
1
6
[ "B6", "B17" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
This model is consistent with a role for the slow-acting SMUG1 in repair of deaminated cytosine in non-replicating chromatin, and efficient and highly coordinated repair by UNG2 of uracil (both U:G and U:A) in replicating DNA.
[ "6", "17" ]
226
6,141
0
false
This model is consistent with a role for the slow-acting SMUG1 in repair of deaminated cytosine in non-replicating chromatin, and efficient and highly coordinated repair by UNG2 of uracil (both U:G and U:A) in replicating DNA.
[]
This model is consistent with a role for the slow-acting SMUG1 in repair of deaminated cytosine in non-replicating chromatin, and efficient and highly coordinated repair by UNG2 of uracil (both U:G and U:A) in replicating DNA.
true
true
true
true
true
1,015
0
DISCUSSION
0
null
null
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
The existence of SMUG1 orthologs in bacteria suggests that SMUG1 is of older origin than previously assumed.
null
108
6,142
0
false
null
null
The existence of SMUG1 orthologs in bacteria suggests that SMUG1 is of older origin than previously assumed.
true
true
true
true
true
1,016
0
DISCUSSION
0
null
null
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Notably, non-vertebrates (except from sea urchin) appear to have UDGs of either the SMUG1- or the UNG-type, while vertebrates contain both.
null
139
6,143
0
false
null
null
Notably, non-vertebrates (except from sea urchin) appear to have UDGs of either the SMUG1- or the UNG-type, while vertebrates contain both.
true
true
true
true
true
1,016
0
DISCUSSION
0
null
null
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
In vertebrates, SMUG1 and UNG2 have probably evolved to carry out different and specialized functions in processing of genomic uracil (and some uracil analogous) in the most appropriate way depending on uracil context, gene locus (e.g.
null
235
6,144
0
false
null
null
In vertebrates, SMUG1 and UNG2 have probably evolved to carry out different and specialized functions in processing of genomic uracil (and some uracil analogous) in the most appropriate way depending on uracil context, gene locus (e.g.
true
true
true
true
true
1,016
0
DISCUSSION
0
null
null
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
Ig-genes), cell type, proliferative status, cell cycle phase, sub-nuclear localization and mutagenic potential of the lesion.
null
125
6,145
0
false
null
null
Ig-genes), cell type, proliferative status, cell cycle phase, sub-nuclear localization and mutagenic potential of the lesion.
true
true
true
true
true
1,016
0
DISCUSSION
0
null
null
17,537,817
pmid-8469282|pmid-15568983|pmid-16908222|pmid-12826402|pmid-14585995
In the present work, we have compared and characterized some of these specialized molecular functions of hSMUG1 and hUNG2 by both in vivo and in vitro experiments, and demonstrated that they coordinate the initial steps in BER by different molecular mechanisms.
null
261
6,146
0
false
null
null
In the present work, we have compared and characterized some of these specialized molecular functions of hSMUG1 and hUNG2 by both in vivo and in vitro experiments, and demonstrated that they coordinate the initial steps in BER by different molecular mechanisms.
true
true
true
true
true
1,016
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
We show that hUNG2, but not hSMUG1, can repair U:G lesions in proliferating E. coli cells in vivo.
[ "27" ]
98
6,147
0
false
We show that hUNG2, but not hSMUG1, can repair U:G lesions in proliferating E. coli cells in vivo.
[]
We show that hUNG2, but not hSMUG1, can repair U:G lesions in proliferating E. coli cells in vivo.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
In contrast, hSMUG1 expression inhibits cell growth in this system.
[ "27" ]
67
6,148
0
false
In contrast, hSMUG1 expression inhibits cell growth in this system.
[]
In contrast, hSMUG1 expression inhibits cell growth in this system.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Interestingly, it was reported that hSMUG1 can functionally compensate for Ung1 in yeast cells treated with antifolate agents to increase misincorporation of uracil in the genome (27).
[ "27" ]
184
6,149
1
false
Interestingly, it was reported that hSMUG1 can functionally compensate for Ung1 in yeast cells treated with antifolate agents to increase misincorporation of uracil in the genome.
[ "27" ]
Interestingly, it was reported that hSMUG1 can functionally compensate for Ung1 in yeast cells treated with antifolate agents to increase misincorporation of uracil in the genome.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
In WT cells, antifolate treatment results in S-phase arrest and cellular toxicity due to uracil excision and single-strand breaks.
[ "27" ]
130
6,150
0
false
In WT cells, antifolate treatment results in S-phase arrest and cellular toxicity due to uracil excision and single-strand breaks.
[]
In WT cells, antifolate treatment results in S-phase arrest and cellular toxicity due to uracil excision and single-strand breaks.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Antifolate-treated ▵ung1 cells are, however, able to complete DNA replication, but when hSMUG1 is expressed the cells are arrested in S-phase like the WT.
[ "27" ]
154
6,151
0
false
Antifolate-treated ▵ung1 cells are, however, able to complete DNA replication, but when hSMUG1 is expressed the cells are arrested in S-phase like the WT.
[]
Antifolate-treated ▵ung1 cells are, however, able to complete DNA replication, but when hSMUG1 is expressed the cells are arrested in S-phase like the WT.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
This indicates that SMUG1 can target misincorporated uracil in the yeast genome and generate cytotoxic AP-sites.
[ "27" ]
112
6,152
0
false
This indicates that SMUG1 can target misincorporated uracil in the yeast genome and generate cytotoxic AP-sites.
[]
This indicates that SMUG1 can target misincorporated uracil in the yeast genome and generate cytotoxic AP-sites.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
However, complete repair of the lesion was not monitored in the yeast study.
[ "27" ]
76
6,153
0
false
However, complete repair of the lesion was not monitored in the yeast study.
[]
However, complete repair of the lesion was not monitored in the yeast study.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Since the authors use S-phase arrest and cellular toxicity as a measure of complementation, their results are in agreement with our results, although their conclusion is different.
[ "27" ]
180
6,154
0
false
Since the authors use S-phase arrest and cellular toxicity as a measure of complementation, their results are in agreement with our results, although their conclusion is different.
[]
Since the authors use S-phase arrest and cellular toxicity as a measure of complementation, their results are in agreement with our results, although their conclusion is different.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
In conclusion, SMUG1 and UNG2 can both target uracil residues, but only UNG2 can initiate complete BER in rapidly growing cells.
[ "27" ]
128
6,155
0
false
In conclusion, SMUG1 and UNG2 can both target uracil residues, but only UNG2 can initiate complete BER in rapidly growing cells.
[]
In conclusion, SMUG1 and UNG2 can both target uracil residues, but only UNG2 can initiate complete BER in rapidly growing cells.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
It cannot be excluded, however, that SMUG1 can compensate for Ung in U:A repair both in yeast and in bacteria.
[ "27" ]
110
6,156
0
false
It cannot be excluded, however, that SMUG1 can compensate for Ung in U:A repair both in yeast and in bacteria.
[]
It cannot be excluded, however, that SMUG1 can compensate for Ung in U:A repair both in yeast and in bacteria.
true
true
true
true
true
1,017
1
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-15902269|pmid-10912000|pmid-15967827|pmid-16407970|pmid-10912000|pmid-9045683|pmid-10393198|pmid-1923798|pmid-9490791|pmid-12161446|pmid-12161446|pmid-11526119|NA|pmid-12820976|pmid-12547394
Furthermore, it would be interesting to find out whether SMUG1 from a prokaryote can complement Ung-deficient bacteria.
[ "27" ]
119
6,157
0
false
Furthermore, it would be interesting to find out whether SMUG1 from a prokaryote can complement Ung-deficient bacteria.
[]
Furthermore, it would be interesting to find out whether SMUG1 from a prokaryote can complement Ung-deficient bacteria.
true
true
true
true
true
1,017
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
We have previously characterized the catalytic domain of hUNG in detail (23,32,33).
[ "23", "32", "33", "41", "7", "38", "41" ]
83
6,158
0
false
We have previously characterized the catalytic domain of hUNG in detail.
[ "23,32,33" ]
We have previously characterized the catalytic domain of hUNG in detail.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Here we generated active site mutants of hSMUG1 and compared their activities with those of the corresponding mutants of hUNG.
[ "23", "32", "33", "41", "7", "38", "41" ]
126
6,159
0
false
Here we generated active site mutants of hSMUG1 and compared their activities with those of the corresponding mutants of hUNG.
[]
Here we generated active site mutants of hSMUG1 and compared their activities with those of the corresponding mutants of hUNG.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Interestingly, using the same standard UDG assay protocol, single active-site mutations in SMUG1 have less effect on catalytic activity than the corresponding mutations in UNG.
[ "23", "32", "33", "41", "7", "38", "41" ]
176
6,160
0
false
Interestingly, using the same standard UDG assay protocol, single active-site mutations in SMUG1 have less effect on catalytic activity than the corresponding mutations in UNG.
[]
Interestingly, using the same standard UDG assay protocol, single active-site mutations in SMUG1 have less effect on catalytic activity than the corresponding mutations in UNG.
true
true
true
true
true
1,018
2
DISCUSSION
1
41
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Analysis of hSMUG1 active-site mutants has also been published by another group (41), and they report a more dramatic reduction in activity of several of the mutants.
[ "23", "32", "33", "41", "7", "38", "41" ]
166
6,161
1
false
Analysis of hSMUG1 active-site mutants has also been published by another group, and they report a more dramatic reduction in activity of several of the mutants.
[ "41" ]
Analysis of hSMUG1 active-site mutants has also been published by another group, and they report a more dramatic reduction in activity of several of the mutants.
true
true
true
true
true
1,018
2
DISCUSSION
1
7
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
This is probably because they measured SMUG1 activity using a very high molar excess of enzyme (up to 670-fold) and substrate concentrations about three orders of magnitude below the Km value of hSMUG1-WT (7) (Figure 7A).
[ "23", "32", "33", "41", "7", "38", "41" ]
221
6,162
1
false
This is probably because they measured SMUG1 activity using a very high molar excess of enzyme and substrate concentrations about three orders of magnitude below the Km value of hSMUG1-WT.
[ "up to 670-fold", "7", "Figure 7A" ]
This is probably because they measured SMUG1 activity using a very high molar excess of enzyme and substrate concentrations about three orders of magnitude below the Km value of hSMUG1-WT.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
Such assay conditions will, however, mainly reflect substrate affinity and not catalytic turnover, because the substrate is the limiting factor.
[ "23", "32", "33", "41", "7", "38", "41" ]
144
6,163
0
false
Such assay conditions will, however, mainly reflect substrate affinity and not catalytic turnover, because the substrate is the limiting factor.
[]
Such assay conditions will, however, mainly reflect substrate affinity and not catalytic turnover, because the substrate is the limiting factor.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
By using a high substrate concentration (1.8 µM), we here focused on catalytic turnover and less on substrate affinity.
[ "23", "32", "33", "41", "7", "38", "41" ]
119
6,164
0
false
By using a high substrate concentration (1.8 µM), we here focused on catalytic turnover and less on substrate affinity.
[]
By using a high substrate concentration (1.8 µM), we here focused on catalytic turnover and less on substrate affinity.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
The relatively high residual uracil-excision activity (measured with molar excess of substrate) in the SMUG1 active-site mutants, especially against U:G substrates, may in part be explained by the specific helix-inserting motif that probably is important for binding to dsDNA substrate and product.
[ "23", "32", "33", "41", "7", "38", "41" ]
298
6,165
0
false
The relatively high residual uracil-excision activity (measured with molar excess of substrate) in the SMUG1 active-site mutants, especially against U:G substrates, may in part be explained by the specific helix-inserting motif that probably is important for binding to dsDNA substrate and product.
[]
The relatively high residual uracil-excision activity (measured with molar excess of substrate) in the SMUG1 active-site mutants, especially against U:G substrates, may in part be explained by the specific helix-inserting motif that probably is important for binding to dsDNA substrate and product.
true
true
true
true
true
1,018
2
DISCUSSION
1
23
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
When SMUG1 is bound to the substrate, the DNA substrate itself may be important to drive the reaction forward by so-called ‘substrate autocatalysis’.
[ "23", "32", "33", "41", "7", "38", "41" ]
149
6,166
0
false
When SMUG1 is bound to the substrate, the DNA substrate itself may be important to drive the reaction forward by so-called ‘substrate autocatalysis’.
[]
When SMUG1 is bound to the substrate, the DNA substrate itself may be important to drive the reaction forward by so-called ‘substrate autocatalysis’.
true
true
true
true
true
1,018
2
DISCUSSION
1
38
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
For glycosylases in the UDG superfamily, it has been reported that the substrate itself is a major contributor to lowering of the activation energy, thus explaining residual activity in mutants lacking catalytic key residues (38).
[ "23", "32", "33", "41", "7", "38", "41" ]
230
6,167
1
false
For glycosylases in the UDG superfamily, it has been reported that the substrate itself is a major contributor to lowering of the activation energy, thus explaining residual activity in mutants lacking catalytic key residues.
[ "38" ]
For glycosylases in the UDG superfamily, it has been reported that the substrate itself is a major contributor to lowering of the activation energy, thus explaining residual activity in mutants lacking catalytic key residues.
true
true
true
true
true
1,018
2
DISCUSSION
1
41
[ "B23", "B32", "B33", "B41", "B7", "B38", "B41" ]
17,537,817
pmid-11483530|NA|pmid-7819187|pmid-8900285|pmid-17116429|pmid-15466595|pmid-12161446|pmid-11607036|pmid-15466595
This ‘substrate autocatalysis’ phenomena may also explain the discrepancy between residual activity of SMUG1 active-site mutants measured at very low substrate concentrations (41) and those presented here measured at high substrate concentrations.
[ "23", "32", "33", "41", "7", "38", "41" ]
247
6,168
1
false
This ‘substrate autocatalysis’ phenomena may also explain the discrepancy between residual activity of SMUG1 active-site mutants measured at very low substrate concentrations and those presented here measured at high substrate concentrations.
[ "41" ]
This ‘substrate autocatalysis’ phenomena may also explain the discrepancy between residual activity of SMUG1 active-site mutants measured at very low substrate concentrations and those presented here measured at high substrate concentrations.
true
true
true
true
true
1,018
3
DISCUSSION
0
null
null
17,537,817
null
Interestingly, one of the active-site SMUG1 mutants was, however, catalytically dead.
null
85
6,169
0
false
null
null
Interestingly, one of the active-site SMUG1 mutants was, however, catalytically dead.
true
true
true
true
true
1,019
3
DISCUSSION
0
null
null
17,537,817
null
Introducing a UNG like thymine expulsion residue in SMUG1 (SMUG1-G87Y) abolished the activity completely.
null
105
6,170
0
false
null
null
Introducing a UNG like thymine expulsion residue in SMUG1 (SMUG1-G87Y) abolished the activity completely.
true
true
true
true
true
1,019
3
DISCUSSION
0
null
null
17,537,817
null
The superimposed structures of xSMUG1 and hUNG reveal that the thymine expulsion loops do not follow the same path, bringing the side-chains of SMUG1-G87Y and UNG-Y147 in different orientation in the substrate binding pockets of the enzymes.
null
241
6,171
0
false
null
null
The superimposed structures of xSMUG1 and hUNG reveal that the thymine expulsion loops do not follow the same path, bringing the side-chains of SMUG1-G87Y and UNG-Y147 in different orientation in the substrate binding pockets of the enzymes.
true
true
true
true
true
1,019
3
DISCUSSION
0
null
null
17,537,817
null
Additionally, in SMUG1 this residue is sandwiched between two prolines that restrict conformational flexibility in this loop segment.
null
133
6,172
0
false
null
null
Additionally, in SMUG1 this residue is sandwiched between two prolines that restrict conformational flexibility in this loop segment.
true
true
true
true
true
1,019
3
DISCUSSION
0
null
null
17,537,817
null
Thus, a large-residue in this position will most likely block the entrance of the substrate in the active site pocket of SMUG1.
null
127
6,173
0
false
null
null
Thus, a large-residue in this position will most likely block the entrance of the substrate in the active site pocket of SMUG1.
true
true
true
true
true
1,019
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
We find that hSMUG1 binds to product AP-sites in dsDNA in vitro, with the strongest binding to AP:G, while no product binding was observed for UNG2.
[ "27" ]
148
6,174
0
false
We find that hSMUG1 binds to product AP-sites in dsDNA in vitro, with the strongest binding to AP:G, while no product binding was observed for UNG2.
[]
We find that hSMUG1 binds to product AP-sites in dsDNA in vitro, with the strongest binding to AP:G, while no product binding was observed for UNG2.
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
The growth-inhibitory effect of SMUG1 in E. coli cells containing U:G lesions is most likely explained by this product binding.
[ "27" ]
127
6,175
0
false
The growth-inhibitory effect of SMUG1 in E. coli cells containing U:G lesions is most likely explained by this product binding.
[]
The growth-inhibitory effect of SMUG1 in E. coli cells containing U:G lesions is most likely explained by this product binding.
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
SMUG1 attached to AP-sites may probably interfere with replication, and thereby prevent cell division, a situation that is especially prominent when SMUG1 is over-expressed.
[ "27" ]
173
6,176
0
false
SMUG1 attached to AP-sites may probably interfere with replication, and thereby prevent cell division, a situation that is especially prominent when SMUG1 is over-expressed.
[]
SMUG1 attached to AP-sites may probably interfere with replication, and thereby prevent cell division, a situation that is especially prominent when SMUG1 is over-expressed.
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
Under these circumstances, the endogenous level of AP-endonuclease activity is likely insufficient to alleviate the product binding and replication is blocked.
[ "27" ]
159
6,177
0
false
Under these circumstances, the endogenous level of AP-endonuclease activity is likely insufficient to alleviate the product binding and replication is blocked.
[]
Under these circumstances, the endogenous level of AP-endonuclease activity is likely insufficient to alleviate the product binding and replication is blocked.
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
In support of this, we find that SMUG1 inhibits activity of both the human APE1 and the bacterial ExoIII AP-endonucleases (Figure 3D).
[ "27" ]
134
6,178
0
false
In support of this, we find that SMUG1 inhibits activity of both the human APE1 and the bacterial ExoIII AP-endonucleases (Figure 3D).
[]
In support of this, we find that SMUG1 inhibits activity of both the human APE1 and the bacterial ExoIII AP-endonucleases (Figure 3D).
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
Thus, a high level of SMUG1 likely interferes with the downstream processing of the AP-sites and prevents complete repair.
[ "27" ]
122
6,179
0
false
Thus, a high level of SMUG1 likely interferes with the downstream processing of the AP-sites and prevents complete repair.
[]
Thus, a high level of SMUG1 likely interferes with the downstream processing of the AP-sites and prevents complete repair.
true
true
true
true
true
1,020
4
DISCUSSION
1
27
[ "B27" ]
17,537,817
pmid-12547394
This is in agreement with the observation that expression of hSMUG1 in Δung1 yeast cells did not suppress the spontaneous mutator phenotype, but rather caused an increased mutation frequency (27).
[ "27" ]
196
6,180
1
false
This is in agreement with the observation that expression of hSMUG1 in Δung1 yeast cells did not suppress the spontaneous mutator phenotype, but rather caused an increased mutation frequency.
[ "27" ]
This is in agreement with the observation that expression of hSMUG1 in Δung1 yeast cells did not suppress the spontaneous mutator phenotype, but rather caused an increased mutation frequency.
true
true
true
true
true
1,020
5
DISCUSSION
1
6
[ "B6", "B7", "B42 B43 B44", "B45" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-11238994|pmid-15713479|pmid-11160897|pmid-15479784
It is well known that APE1 stimulates the excision activity of many DNA glycosylases (6,7,42–44).
[ "6", "7", "42–44", "45" ]
97
6,181
0
false
It is well known that APE1 stimulates the excision activity of many DNA glycosylases.
[ "6,7,42–44" ]
It is well known that APE1 stimulates the excision activity of many DNA glycosylases.
true
true
true
true
true
1,021
5
DISCUSSION
1
6
[ "B6", "B7", "B42 B43 B44", "B45" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-11238994|pmid-15713479|pmid-11160897|pmid-15479784
However, stimulation of APE1 by a DNA-glycosylase has to our knowledge not previously been reported.
[ "6", "7", "42–44", "45" ]
100
6,182
0
false
However, stimulation of APE1 by a DNA-glycosylase has to our knowledge not previously been reported.
[]
However, stimulation of APE1 by a DNA-glycosylase has to our knowledge not previously been reported.
true
true
true
true
true
1,021
5
DISCUSSION
1
6
[ "B6", "B7", "B42 B43 B44", "B45" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-11238994|pmid-15713479|pmid-11160897|pmid-15479784
Here we find that UNG2 stimulates the cleavage activity of APE1, indicating that UNG2 may physically interact with APE1.
[ "6", "7", "42–44", "45" ]
120
6,183
0
false
Here we find that UNG2 stimulates the cleavage activity of APE1, indicating that UNG2 may physically interact with APE1.
[]
Here we find that UNG2 stimulates the cleavage activity of APE1, indicating that UNG2 may physically interact with APE1.
true
true
true
true
true
1,021
5
DISCUSSION
1
45
[ "B6", "B7", "B42 B43 B44", "B45" ]
17,537,817
pmid-11483530|pmid-12161446|pmid-11238994|pmid-15713479|pmid-11160897|pmid-15479784
In support of this, we have previously isolated UNG2-associated complexes containing all factors required for complete BER of uracil, including APE1, from human cell extracts (45).
[ "6", "7", "42–44", "45" ]
180
6,184
1
false
In support of this, we have previously isolated UNG2-associated complexes containing all factors required for complete BER of uracil, including APE1, from human cell extracts.
[ "45" ]
In support of this, we have previously isolated UNG2-associated complexes containing all factors required for complete BER of uracil, including APE1, from human cell extracts.
true
true
true
true
true
1,021
6
DISCUSSION
1
23
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
We have examined whether sequence context of the substrate influenced on uracil-excision activity of SMUG1 and UNG2.
[ "23", "46", "47", "48", "7", "20", "49" ]
116
6,185
0
false
We have examined whether sequence context of the substrate influenced on uracil-excision activity of SMUG1 and UNG2.
[]
We have examined whether sequence context of the substrate influenced on uracil-excision activity of SMUG1 and UNG2.
true
true
true
true
true
1,022
6
DISCUSSION
1
23
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
Surprisingly, the nature of the bases flanking the uracil had only impact on uracil-excision activity of SMUG1 and not of UNG2, measured on the same double-stranded oligonucleotide substrates.
[ "23", "46", "47", "48", "7", "20", "49" ]
192
6,186
0
false
Surprisingly, the nature of the bases flanking the uracil had only impact on uracil-excision activity of SMUG1 and not of UNG2, measured on the same double-stranded oligonucleotide substrates.
[]
Surprisingly, the nature of the bases flanking the uracil had only impact on uracil-excision activity of SMUG1 and not of UNG2, measured on the same double-stranded oligonucleotide substrates.
true
true
true
true
true
1,022
6
DISCUSSION
1
48
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
The latter was rather unexpected since sequence preference of UNG from several sources [a truncated form of UNG purified from calf thymus, E. coli Ung and the catalytic domain of human UNG (UNGΔ84)] has previously been demonstrated in our laboratory (23,46,47) and by others (herpes simplex virus UDG) (48).
[ "23", "46", "47", "48", "7", "20", "49" ]
307
6,187
1
false
The latter was rather unexpected since sequence preference of UNG from several sources [a truncated form of UNG purified from calf thymus, E. coli Ung and the catalytic domain of human UNG (UNGΔ84)] has previously been demonstrated in our laboratory and by others (herpes simplex virus UDG).
[ "23,46,47", "48" ]
The latter was rather unexpected since sequence preference of UNG from several sources has previously been demonstrated in our laboratory and by others (herpes simplex virus UDG).
true
true
true
true
true
1,022
6
DISCUSSION
1
23
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
However, all these enzymes lack the regulatory N-terminal sequence.
[ "23", "46", "47", "48", "7", "20", "49" ]
67
6,188
0
false
However, all these enzymes lack the regulatory N-terminal sequence.
[]
However, all these enzymes lack the regulatory N-terminal sequence.
true
true
true
true
true
1,022
6
DISCUSSION
1
23
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
In the present study we have analysed the full-length human UNG2 enzyme in presence of Mg2+, which has a strong stimulatory effect particularly on UNG2 (7,20,49).
[ "23", "46", "47", "48", "7", "20", "49" ]
162
6,189
0
false
In the present study we have analysed the full-length human UNG2 enzyme in presence of Mg2+, which has a strong stimulatory effect particularly on UNG2.
[ "7,20,49" ]
In the present study we have analysed the full-length human UNG2 enzyme in presence of Mg2+, which has a strong stimulatory effect particularly on UNG2.
true
true
true
true
true
1,022
6
DISCUSSION
1
23
[ "B23", "B46", "B47", "B48", "B7", "B20", "B49" ]
17,537,817
pmid-7819187|pmid-8502549|pmid-7720873|pmid-11557818|pmid-12161446|pmid-12907738|pmid-16216562
It is possible that the N-terminal domain of UNG2 diminishes the sequence specificity observed for the truncated forms of UNG in order to obtain the most efficient repair of uracil in all contexts at the replication fork.
[ "23", "46", "47", "48", "7", "20", "49" ]
221
6,190
0
false
It is possible that the N-terminal domain of UNG2 diminishes the sequence specificity observed for the truncated forms of UNG in order to obtain the most efficient repair of uracil in all contexts at the replication fork.
[]
It is possible that the N-terminal domain of UNG2 diminishes the sequence specificity observed for the truncated forms of UNG in order to obtain the most efficient repair of uracil in all contexts at the replication fork.
true
true
true
true
true
1,022
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
Taken together, it is clear that SMUG1 and UNG2 have evolved distinct mechanisms for the coordination of the second step in BER.
[ "13", "8", "15", "8" ]
128
6,191
0
false
Taken together, it is clear that SMUG1 and UNG2 have evolved distinct mechanisms for the coordination of the second step in BER.
[]
Taken together, it is clear that SMUG1 and UNG2 have evolved distinct mechanisms for the coordination of the second step in BER.
true
true
true
true
true
1,023
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
Based on previous results and the new data presented here, we propose a model for how SMUG1 and UNG2 initiates and coordinates repair of deaminated cytosine (U:G) by distinct ‘hand-over’ mechanisms (Figure 8).
[ "13", "8", "15", "8" ]
209
6,192
0
false
Based on previous results and the new data presented here, we propose a model for how SMUG1 and UNG2 initiates and coordinates repair of deaminated cytosine (U:G) by distinct ‘hand-over’ mechanisms.
[ "Figure 8" ]
Based on previous results and the new data presented here, we propose a model for how SMUG1 and UNG2 initiates and coordinates repair of deaminated cytosine (U:G) by distinct ‘hand-over’ mechanisms.
true
true
true
true
true
1,023
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
This model is consistent with a role for SMUG1 in repair of deaminated cytosine in non-replicating chromatin and repair of uracil (U:G and U:A) by UNG2 in replication foci.
[ "13", "8", "15", "8" ]
172
6,193
0
false
This model is consistent with a role for SMUG1 in repair of deaminated cytosine in non-replicating chromatin and repair of uracil (U:G and U:A) by UNG2 in replication foci.
[]
This model is consistent with a role for SMUG1 in repair of deaminated cytosine in non-replicating chromatin and repair of uracil (U:G and U:A) by UNG2 in replication foci.
true
true
true
true
true
1,023
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
The catalytically highly efficient and context-independent UNG2 enzyme is probably important in rapidly dividing cells to remove deaminated cytosine in front of the moving replication fork (pre-replicative repair), in addition to post-replicative repair of misincorporated uracil (13).
[ "13", "8", "15", "8" ]
285
6,194
1
false
The catalytically highly efficient and context-independent UNG2 enzyme is probably important in rapidly dividing cells to remove deaminated cytosine in front of the moving replication fork (pre-replicative repair), in addition to post-replicative repair of misincorporated uracil.
[ "13" ]
The catalytically highly efficient and context-independent UNG2 enzyme is probably important in rapidly dividing cells to remove deaminated cytosine in front of the moving replication fork (pre-replicative repair), in addition to post-replicative repair of misincorporated uracil.
true
true
true
true
true
1,023
7
DISCUSSION
1
8
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
This pre-replicative repair of U:G by UNG2 is supported by the observed 5.2-fold increased mutation frequency in Ung-deficient mouse embryonic fibroblasts (MEFs), mostly G:C to A:T transitions (8).
[ "13", "8", "15", "8" ]
197
6,195
1
false
This pre-replicative repair of U:G by UNG2 is supported by the observed 5.2-fold increased mutation frequency in Ung-deficient mouse embryonic fibroblasts (MEFs), mostly G:C to A:T transitions.
[ "8" ]
This pre-replicative repair of U:G by UNG2 is supported by the observed 5.2-fold increased mutation frequency in Ung-deficient mouse embryonic fibroblasts (MEFs), mostly G:C to A:T transitions.
true
true
true
true
true
1,023
7
DISCUSSION
1
15
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
SMUG1, on the other hand, is not designed to rapidly repair uracil during replication, and is probably more important in non-replicating chromatin, outside S-phase and in resting cells where the level of UNG2 is low (15).
[ "13", "8", "15", "8" ]
221
6,196
1
false
SMUG1, on the other hand, is not designed to rapidly repair uracil during replication, and is probably more important in non-replicating chromatin, outside S-phase and in resting cells where the level of UNG2 is low.
[ "15" ]
SMUG1, on the other hand, is not designed to rapidly repair uracil during replication, and is probably more important in non-replicating chromatin, outside S-phase and in resting cells where the level of UNG2 is low.
true
true
true
true
true
1,023
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
However, SMUG1 counteracts mutations also in cycling mouse cells (MEFs).
[ "13", "8", "15", "8" ]
72
6,197
0
false
However, SMUG1 counteracts mutations also in cycling mouse cells (MEFs).
[]
However, SMUG1 counteracts mutations also in cycling mouse cells (MEFs).
true
true
true
true
true
1,023
7
DISCUSSION
1
8
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
Knocking down Smug1 by siRNA in MEFs resulted in 2.4-fold increased mutation frequency at the HPRT locus (8).
[ "13", "8", "15", "8" ]
109
6,198
1
false
Knocking down Smug1 by siRNA in MEFs resulted in 2.4-fold increased mutation frequency at the HPRT locus.
[ "8" ]
Knocking down Smug1 by siRNA in MEFs resulted in 2.4-fold increased mutation frequency at the HPRT locus.
true
true
true
true
true
1,023
7
DISCUSSION
1
13
[ "B13", "B8", "B15", "B8" ]
17,537,817
pmid-10393198|pmid-15902269|pmid-9490791|pmid-15902269
Thus, the slow-acting, product-binding SMUG1 may efficiently recognize deaminated and some oxidized cytosine derivatives in non-replicating dsDNA (especially in A-T rich regions where the cytosine deamination rate is expected to be higher due to increased DNA breathing), excise the lesion and remain attached to the cyt...
[ "13", "8", "15", "8" ]
391
6,199
0
false
Thus, the slow-acting, product-binding SMUG1 may efficiently recognize deaminated and some oxidized cytosine derivatives in non-replicating dsDNA (especially in A-T rich regions where the cytosine deamination rate is expected to be higher due to increased DNA breathing), excise the lesion and remain attached to the cyt...
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Thus, the slow-acting, product-binding SMUG1 may efficiently recognize deaminated and some oxidized cytosine derivatives in non-replicating dsDNA (especially in A-T rich regions where the cytosine deamination rate is expected to be higher due to increased DNA breathing), excise the lesion and remain attached to the cyt...
true
true
true
true
true
1,023