Datasets:
vgainullin
/
xciting_data

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4
INTRODUCTION
1
38
[ "B38", "B23", "B39", "B40" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
These comparisons of mutation rate and spectrum in this model genetic system reveal fundamental differences between the contributions of the FA and HRR pathways in preventing mutagenesis.
[ "38", "23", "39", "40" ]
187
11,600
0
false
These comparisons of mutation rate and spectrum in this model genetic system reveal fundamental differences between the contributions of the FA and HRR pathways in preventing mutagenesis.
[]
These comparisons of mutation rate and spectrum in this model genetic system reveal fundamental differences between the contributions of the FA and HRR pathways in preventing mutagenesis.
true
true
true
true
true
1,859
4
INTRODUCTION
1
38
[ "B38", "B23", "B39", "B40" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
Our findings suggest that the FA pathway may deal with spontaneous DNA damage by promoting efficient DNA end joining as well as TLS and HRR.
[ "38", "23", "39", "40" ]
140
11,601
0
false
Our findings suggest that the FA pathway may deal with spontaneous DNA damage by promoting efficient DNA end joining as well as TLS and HRR.
[]
Our findings suggest that the FA pathway may deal with spontaneous DNA damage by promoting efficient DNA end joining as well as TLS and HRR.
true
true
true
true
true
1,859
0
DISCUSSION
1
23
[ "B23", "B53" ]
17,517,774
pmid-8892734|pmid-11389461|pmid-16132046|pmid-16377561|pmid-16357213|pmid-17289582|pmid-17396147|pmid-12239151|pmid-11376695|pmid-14643432|pmid-15723711|pmid-12065746|pmid-16621732|pmid-16522646|pmid-16055725
In the rad51d cells, the greatly increased yield of hprt mutants suggests a prominent role for this pathway in preventing frequent mutagenic events from occurring during normal DNA replication in the face of spontaneous (oxidative) lesions (23).
[ "23", "53" ]
245
11,602
1
false
In the rad51d cells, the greatly increased yield of hprt mutants suggests a prominent role for this pathway in preventing frequent mutagenic events from occurring during normal DNA replication in the face of spontaneous (oxidative) lesions.
[ "23" ]
In the rad51d cells, the greatly increased yield of hprt mutants suggests a prominent role for this pathway in preventing frequent mutagenic events from occurring during normal DNA replication in the face of spontaneous (oxidative) lesions.
true
true
true
true
true
1,860
0
DISCUSSION
1
53
[ "B23", "B53" ]
17,517,774
pmid-8892734|pmid-11389461|pmid-16132046|pmid-16377561|pmid-16357213|pmid-17289582|pmid-17396147|pmid-12239151|pmid-11376695|pmid-14643432|pmid-15723711|pmid-12065746|pmid-16621732|pmid-16522646|pmid-16055725
Indeed, HRR was shown to act on collapsed replication forks caused by endogenous DNA single-strand breaks (53).
[ "23", "53" ]
111
11,603
1
false
Indeed, HRR was shown to act on collapsed replication forks caused by endogenous DNA single-strand breaks.
[ "53" ]
Indeed, HRR was shown to act on collapsed replication forks caused by endogenous DNA single-strand breaks.
true
true
true
true
true
1,860
0
DISCUSSION
1
23
[ "B23", "B53" ]
17,517,774
pmid-8892734|pmid-11389461|pmid-16132046|pmid-16377561|pmid-16357213|pmid-17289582|pmid-17396147|pmid-12239151|pmid-11376695|pmid-14643432|pmid-15723711|pmid-12065746|pmid-16621732|pmid-16522646|pmid-16055725
In our study we found that the spectrum of mutations from rad51d cells reveals that the mutagenic events prevented by intact HRR are deletions, likely caused by efficient DNA end-joining mechanisms that repair DSBs that persist when broken replication forks are not restarted.
[ "23", "53" ]
276
11,604
0
false
In our study we found that the spectrum of mutations from rad51d cells reveals that the mutagenic events prevented by intact HRR are deletions, likely caused by efficient DNA end-joining mechanisms that repair DSBs that persist when broken replication forks are not restarted.
[]
In our study we found that the spectrum of mutations from rad51d cells reveals that the mutagenic events prevented by intact HRR are deletions, likely caused by efficient DNA end-joining mechanisms that repair DSBs that persist when broken replication forks are not restarted.
true
true
true
true
true
1,860
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
In the fancg CHO cells, we see a major reduction in the yield of four classes of spontaneous hprt mutants compared with wild-type.
[ "45–47" ]
130
11,605
0
false
In the fancg CHO cells, we see a major reduction in the yield of four classes of spontaneous hprt mutants compared with wild-type.
[]
In the fancg CHO cells, we see a major reduction in the yield of four classes of spontaneous hprt mutants compared with wild-type.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
The reduced yield of both base substitution and deletion/insertion events in the fancg cells points to a role for Fancg and the FA proteins in promoting TLS at replication-blocking lesions (the source of base substitution mutations), as well as in coordinating HRR to restart broken replication forks and NHEJ to restore...
[ "45–47" ]
349
11,606
0
false
The reduced yield of both base substitution and deletion/insertion events in the fancg cells points to a role for Fancg and the FA proteins in promoting TLS at replication-blocking lesions (the source of base substitution mutations), as well as in coordinating HRR to restart broken replication forks and NHEJ to restore...
[]
The reduced yield of both base substitution and deletion/insertion events in the fancg cells points to a role for Fancg and the FA proteins in promoting TLS at replication-blocking lesions (the source of base substitution mutations), as well as in coordinating HRR to restart broken replication forks and NHEJ to restore...
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
The latter two processes are necessary events for assuring either conservative repair or recoverable hprt deletion mutants, respectively.
[ "45–47" ]
137
11,607
0
false
The latter two processes are necessary events for assuring either conservative repair or recoverable hprt deletion mutants, respectively.
[]
The latter two processes are necessary events for assuring either conservative repair or recoverable hprt deletion mutants, respectively.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
There was a tendency toward more deletions among spontaneous mutations of the CHO fancg cells.
[ "45–47" ]
94
11,608
0
false
There was a tendency toward more deletions among spontaneous mutations of the CHO fancg cells.
[]
There was a tendency toward more deletions among spontaneous mutations of the CHO fancg cells.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
It is interesting to note that the spectrum of spontaneous mutations in hprt in FA lymphoblasts and T-lymphocytes is also shifted toward more frequent deletions versus base substitutions (45–47).
[ "45–47" ]
195
11,609
1
false
It is interesting to note that the spectrum of spontaneous mutations in hprt in FA lymphoblasts and T-lymphocytes is also shifted toward more frequent deletions versus base substitutions.
[ "45–47" ]
It is interesting to note that the spectrum of spontaneous mutations in hprt in FA lymphoblasts and T-lymphocytes is also shifted toward more frequent deletions versus base substitutions.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
In the fancg cells a high proportion of replication fork breaks, which in normal or rad51d cells often result in recoverable hprt mutants, must result in lethality to account for the reduced yield of viable mutants.
[ "45–47" ]
215
11,610
0
false
In the fancg cells a high proportion of replication fork breaks, which in normal or rad51d cells often result in recoverable hprt mutants, must result in lethality to account for the reduced yield of viable mutants.
[]
In the fancg cells a high proportion of replication fork breaks, which in normal or rad51d cells often result in recoverable hprt mutants, must result in lethality to account for the reduced yield of viable mutants.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
The most likely source of this reduction is the failure to rejoin the breaks due to both impaired HRR and end joining, or by erroneous rejoining causing multigenic, lethal deletion or translocation (as depicted by the model in Figure 3 and discussed subsequently).
[ "45–47" ]
264
11,611
0
false
The most likely source of this reduction is the failure to rejoin the breaks due to both impaired HRR and end joining, or by erroneous rejoining causing multigenic, lethal deletion or translocation (as depicted by the model in Figure 3 and discussed subsequently).
[]
The most likely source of this reduction is the failure to rejoin the breaks due to both impaired HRR and end joining, or by erroneous rejoining causing multigenic, lethal deletion or translocation (as depicted by the model in Figure 3 and discussed subsequently).
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Figure 3.Model of spontaneous hprt mutational outcome in wild-type, rad51d and fancg mutant cells during replication.
[ "45–47" ]
117
11,612
0
false
Figure 3.Model of spontaneous hprt mutational outcome in wild-type, rad51d and fancg mutant cells during replication.
[]
Figure 3.Model of spontaneous hprt mutational outcome in wild-type, rad51d and fancg mutant cells during replication.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Each panel represents one of the three genotypes: wild type, rad51d and fancg.
[ "45–47" ]
78
11,613
0
false
Each panel represents one of the three genotypes: wild type, rad51d and fancg.
[]
Each panel represents one of the three genotypes: wild type, rad51d and fancg.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
On the right in each panel are shown the potential mutational outcomes due to a replication fork encountering a polymerase-blocking lesion (upper fork) or a single-strand break or gap such as a repair intermediate (lower fork).
[ "45–47" ]
227
11,614
0
false
On the right in each panel are shown the potential mutational outcomes due to a replication fork encountering a polymerase-blocking lesion (upper fork) or a single-strand break or gap such as a repair intermediate (lower fork).
[]
On the right in each panel are shown the potential mutational outcomes due to a replication fork encountering a polymerase-blocking lesion (upper fork) or a single-strand break or gap such as a repair intermediate (lower fork).
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Arrows represent the options for resolving each situation, leading to the viable or lethal mutagenic events.
[ "45–47" ]
108
11,615
0
false
Arrows represent the options for resolving each situation, leading to the viable or lethal mutagenic events.
[]
Arrows represent the options for resolving each situation, leading to the viable or lethal mutagenic events.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Upper panel:
[ "45–47" ]
12
11,616
0
false
Upper panel:
[]
Upper panel:
true
true
false
true
false
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
In wild-type cells, there are two major outcomes (large green arrows): translesion synthesis (TLS) bypasses fork blocking lesions (sometimes leading to base substitution, β€˜m’), and homologous recombination (HR) restarts broken replication forks and prevents mutations.
[ "45–47" ]
268
11,617
0
false
In wild-type cells, there are two major outcomes (large green arrows): translesion synthesis (TLS) bypasses fork blocking lesions (sometimes leading to base substitution, β€˜m’), and homologous recombination (HR) restarts broken replication forks and prevents mutations.
[]
In wild-type cells, there are two major outcomes (large green arrows): translesion synthesis (TLS) bypasses fork blocking lesions (sometimes leading to base substitution, β€˜m’), and homologous recombination (HR) restarts broken replication forks and prevents mutations.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Middle panel: The HR-defective rad51d cells, which are presumed to have normal TLS, inefficiently restart broken forks in an error-free manner, but retain efficient NHEJ activity, as evidenced by a high frequency and proportion of small-sized (non-lethal) deletions (large red arrow).
[ "45–47" ]
284
11,618
0
false
Middle panel: The HR-defective rad51d cells, which are presumed to have normal TLS, inefficiently restart broken forks in an error-free manner, but retain efficient NHEJ activity, as evidenced by a high frequency and proportion of small-sized (non-lethal) deletions (large red arrow).
[]
Middle panel: The HR-defective rad51d cells, which are presumed to have normal TLS, inefficiently restart broken forks in an error-free manner, but retain efficient NHEJ activity, as evidenced by a high frequency and proportion of small-sized (non-lethal) deletions (large red arrow).
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
NHEJ acts on replication-associated DSBs that arise when replication forks break and free-ends persist as replication continues.
[ "45–47" ]
128
11,619
0
false
NHEJ acts on replication-associated DSBs that arise when replication forks break and free-ends persist as replication continues.
[]
NHEJ acts on replication-associated DSBs that arise when replication forks break and free-ends persist as replication continues.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
Lower panel: In the fancg cells, the reduced absolute number of base substitutions and small deletions, along with the increased rate of gene amplification, suggest diminished TLS and HR, as well as the loss of NHEJ activity that produces deletions that are recoverable in the hprt mutagenesis assay (as in rad51d cells)...
[ "45–47" ]
321
11,620
0
false
Lower panel: In the fancg cells, the reduced absolute number of base substitutions and small deletions, along with the increased rate of gene amplification, suggest diminished TLS and HR, as well as the loss of NHEJ activity that produces deletions that are recoverable in the hprt mutagenesis assay (as in rad51d cells)...
[]
Lower panel: In the fancg cells, the reduced absolute number of base substitutions and small deletions, along with the increased rate of gene amplification, suggest diminished TLS and HR, as well as the loss of NHEJ activity that produces deletions that are recoverable in the hprt mutagenesis assay.
true
true
true
true
true
1,861
1
DISCUSSION
1
45–47
[ "B45 B46 B47" ]
17,517,774
NA|pmid-11389461|pmid-12509764|pmid-15084315|pmid-15668941|pmid-14726021|pmid-15907771|pmid-14522929|pmid-15498778|pmid-15723711|pmid-12427531|pmid-16522646|pmid-12861027|pmid-15601828|pmid-15650050|pmid-9287344|pmid-12748186|pmid-15671039|pmid-2159378|pmid-2236046|pmid-10635999
The predominant events in fancg cells appear to be inviable deletions or rearrangements (large red arrow).
[ "45–47" ]
106
11,621
0
false
The predominant events in fancg cells appear to be inviable deletions or rearrangements (large red arrow).
[]
The predominant events in fancg cells appear to be inviable deletions or rearrangements (large red arrow).
true
true
true
true
true
1,861
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Model of spontaneous hprt mutational outcome in wild-type, rad51d and fancg mutant cells during replication.
null
108
11,622
0
false
null
null
Model of spontaneous hprt mutational outcome in wild-type, rad51d and fancg mutant cells during replication.
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Each panel represents one of the three genotypes: wild type, rad51d and fancg.
null
78
11,623
0
false
null
null
Each panel represents one of the three genotypes: wild type, rad51d and fancg.
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
On the right in each panel are shown the potential mutational outcomes due to a replication fork encountering a polymerase-blocking lesion (upper fork) or a single-strand break or gap such as a repair intermediate (lower fork).
null
227
11,624
0
false
null
null
On the right in each panel are shown the potential mutational outcomes due to a replication fork encountering a polymerase-blocking lesion (upper fork) or a single-strand break or gap such as a repair intermediate (lower fork).
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Arrows represent the options for resolving each situation, leading to the viable or lethal mutagenic events.
null
108
11,625
0
false
null
null
Arrows represent the options for resolving each situation, leading to the viable or lethal mutagenic events.
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Upper panel:
null
12
11,626
0
false
null
null
Upper panel:
true
true
false
true
false
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
In wild-type cells, there are two major outcomes (large green arrows): translesion synthesis (TLS) bypasses fork blocking lesions (sometimes leading to base substitution, β€˜m’), and homologous recombination (HR) restarts broken replication forks and prevents mutations.
null
268
11,627
0
false
null
null
In wild-type cells, there are two major outcomes (large green arrows): translesion synthesis (TLS) bypasses fork blocking lesions (sometimes leading to base substitution, β€˜m’), and homologous recombination (HR) restarts broken replication forks and prevents mutations.
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Middle panel: The HR-defective rad51d cells, which are presumed to have normal TLS, inefficiently restart broken forks in an error-free manner, but retain efficient NHEJ activity, as evidenced by a high frequency and proportion of small-sized (non-lethal) deletions (large red arrow).
null
284
11,628
0
false
null
null
Middle panel: The HR-defective rad51d cells, which are presumed to have normal TLS, inefficiently restart broken forks in an error-free manner, but retain efficient NHEJ activity, as evidenced by a high frequency and proportion of small-sized (non-lethal) deletions (large red arrow).
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
NHEJ acts on replication-associated DSBs that arise when replication forks break and free-ends persist as replication continues.
null
128
11,629
0
false
null
null
NHEJ acts on replication-associated DSBs that arise when replication forks break and free-ends persist as replication continues.
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
Lower panel: In the fancg cells, the reduced absolute number of base substitutions and small deletions, along with the increased rate of gene amplification, suggest diminished TLS and HR, as well as the loss of NHEJ activity that produces deletions that are recoverable in the hprt mutagenesis assay (as in rad51d cells)...
null
321
11,630
0
false
null
null
Lower panel: In the fancg cells, the reduced absolute number of base substitutions and small deletions, along with the increased rate of gene amplification, suggest diminished TLS and HR, as well as the loss of NHEJ activity that produces deletions that are recoverable in the hprt mutagenesis assay (as in rad51d cells)...
true
true
true
true
true
1,862
2
DISCUSSION
0
null
null
17,517,774
pmid-15650050|pmid-11124945|pmid-12361951|pmid-15199173
The predominant events in fancg cells appear to be inviable deletions or rearrangements (large red arrow).
null
106
11,631
0
false
null
null
The predominant events in fancg cells appear to be inviable deletions or rearrangements (large red arrow).
true
true
true
true
true
1,862
3
DISCUSSION
1
54
[ "B54", "B55", "B55 B56 B57 B58", "B52", "B51", "B23" ]
17,517,774
pmid-16522646|pmid-16522646|NA|pmid-7689157|pmid-15822129|pmid-16166284|pmid-15327776|pmid-2687881|pmid-16787682|pmid-16787682|pmid-8868464|pmid-9566927|pmid-10859355|pmid-12509235|pmid-11389084|pmid-16522646
Gene amplification is a type of mutation often associated with tumors and is elevated in cultured tumor cells versus non-tumorigenic cells (54,55).
[ "54", "55", "55–58", "52", "51", "23" ]
147
11,632
0
false
Gene amplification is a type of mutation often associated with tumors and is elevated in cultured tumor cells versus non-tumorigenic cells.
[ "54,55" ]
Gene amplification is a type of mutation often associated with tumors and is elevated in cultured tumor cells versus non-tumorigenic cells.
true
true
true
true
true
1,863
3
DISCUSSION
1
55–58
[ "B54", "B55", "B55 B56 B57 B58", "B52", "B51", "B23" ]
17,517,774
pmid-16522646|pmid-16522646|NA|pmid-7689157|pmid-15822129|pmid-16166284|pmid-15327776|pmid-2687881|pmid-16787682|pmid-16787682|pmid-8868464|pmid-9566927|pmid-10859355|pmid-12509235|pmid-11389084|pmid-16522646
Many studies have shown the importance of DSBs in gene amplification although the mechanisms remain incompletely understood (55–58).
[ "54", "55", "55–58", "52", "51", "23" ]
132
11,633
1
false
Many studies have shown the importance of DSBs in gene amplification although the mechanisms remain incompletely understood.
[ "55–58" ]
Many studies have shown the importance of DSBs in gene amplification although the mechanisms remain incompletely understood.
true
true
true
true
true
1,863
3
DISCUSSION
1
52
[ "B54", "B55", "B55 B56 B57 B58", "B52", "B51", "B23" ]
17,517,774
pmid-16522646|pmid-16522646|NA|pmid-7689157|pmid-15822129|pmid-16166284|pmid-15327776|pmid-2687881|pmid-16787682|pmid-16787682|pmid-8868464|pmid-9566927|pmid-10859355|pmid-12509235|pmid-11389084|pmid-16522646
Treatments with IR or H2O2, which cause lesions that include DSBs, enhance gene amplification (52).
[ "54", "55", "55–58", "52", "51", "23" ]
99
11,634
1
false
Treatments with IR or H2O2, which cause lesions that include DSBs, enhance gene amplification.
[ "52" ]
Treatments with IR or H2O2, which cause lesions that include DSBs, enhance gene amplification.
true
true
true
true
true
1,863
3
DISCUSSION
1
51
[ "B54", "B55", "B55 B56 B57 B58", "B52", "B51", "B23" ]
17,517,774
pmid-16522646|pmid-16522646|NA|pmid-7689157|pmid-15822129|pmid-16166284|pmid-15327776|pmid-2687881|pmid-16787682|pmid-16787682|pmid-8868464|pmid-9566927|pmid-10859355|pmid-12509235|pmid-11389084|pmid-16522646
CHO cells defective in NHEJ due to a DNA-PKcs mutation have greatly elevated (20- to 150-fold) amplification (51), while the rad51d cells show 4- to 10-fold increases (23).
[ "54", "55", "55–58", "52", "51", "23" ]
172
11,635
1
false
CHO cells defective in NHEJ due to a DNA-PKcs mutation have greatly elevated (20- to 150-fold) amplification, while the rad51d cells show 4- to 10-fold increases.
[ "51", "23" ]
CHO cells defective in NHEJ due to a DNA-PKcs mutation have greatly elevated amplification, while the rad51d cells show 4- to 10-fold increases.
true
true
true
true
true
1,863
4
DISCUSSION
1
59
[ "B59" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
Our findings of 3- to 4-fold increased gene amplification in the fancg cells support the idea that DSBs arising during DNA replication are aberrantly repaired.
[ "59" ]
159
11,636
0
false
Our findings of 3- to 4-fold increased gene amplification in the fancg cells support the idea that DSBs arising during DNA replication are aberrantly repaired.
[]
Our findings of 3- to 4-fold increased gene amplification in the fancg cells support the idea that DSBs arising during DNA replication are aberrantly repaired.
true
true
true
true
true
1,864
4
DISCUSSION
1
59
[ "B59" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
The breakage–fusion-bridge mechanism of amplification is a popular model (59), in which the amplification process may be initiated by a DSB that arises during replication and persists until being removed by end joining between sister chromatids.
[ "59" ]
245
11,637
1
false
The breakage–fusion-bridge mechanism of amplification is a popular model, in which the amplification process may be initiated by a DSB that arises during replication and persists until being removed by end joining between sister chromatids.
[ "59" ]
The breakage–fusion-bridge mechanism of amplification is a popular model, in which the amplification process may be initiated by a DSB that arises during replication and persists until being removed by end joining between sister chromatids.
true
true
true
true
true
1,864
4
DISCUSSION
1
59
[ "B59" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
During the next anaphase, an asymmetrical mechanical break in the dicentric β€˜bridge’ chromosome can then result in duplication of the target gene in one daughter cell.
[ "59" ]
167
11,638
0
false
During the next anaphase, an asymmetrical mechanical break in the dicentric β€˜bridge’ chromosome can then result in duplication of the target gene in one daughter cell.
[]
During the next anaphase, an asymmetrical mechanical break in the dicentric β€˜bridge’ chromosome can then result in duplication of the target gene in one daughter cell.
true
true
true
true
true
1,864
4
DISCUSSION
1
59
[ "B59" ]
17,517,774
pmid-15533833|pmid-16522646|pmid-927508|pmid-6273843|pmid-15561104
This process can be repeated in subsequent mitoses.
[ "59" ]
51
11,639
0
false
This process can be repeated in subsequent mitoses.
[]
This process can be repeated in subsequent mitoses.
true
true
true
true
true
1,864
5
DISCUSSION
1
38
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
It is noteworthy that fancg CHO cells are hypersensitive to killing by a variety of mutagens besides crosslinking agents, i.e.
[ "38", "33", "38" ]
126
11,640
0
false
It is noteworthy that fancg CHO cells are hypersensitive to killing by a variety of mutagens besides crosslinking agents, i.e.
[]
It is noteworthy that fancg CHO cells are hypersensitive to killing by a variety of mutagens besides crosslinking agents, i.e.
true
true
true
true
true
1,865
5
DISCUSSION
1
38
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
Ξ³-rays, methyl methanesulfonate, methylnitrosourea, ethylnitrosourea and 6S-Gua (38).
[ "38", "33", "38" ]
85
11,641
1
false
Ξ³-rays, methyl methanesulfonate, methylnitrosourea, ethylnitrosourea and 6S-Gua.
[ "38" ]
Ξ³-rays, methyl methanesulfonate, methylnitrosourea, ethylnitrosourea and 6S-Gua.
false
true
true
true
false
1,865
5
DISCUSSION
1
38
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
This finding implies that loss of Fancg and, consequently, Fancd2 monoubiquitination, causes a defect in dealing with a much broader class of DNA damage than simply inter-strand crosslinking, e.g.
[ "38", "33", "38" ]
196
11,642
0
false
This finding implies that loss of Fancg and, consequently, Fancd2 monoubiquitination, causes a defect in dealing with a much broader class of DNA damage than simply inter-strand crosslinking, e.g.
[]
This finding implies that loss of Fancg and, consequently, Fancd2 monoubiquitination, causes a defect in dealing with a much broader class of DNA damage than simply inter-strand crosslinking, e.g.
true
true
true
true
true
1,865
5
DISCUSSION
1
38
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
oxidative and alkylation lesions commonly caused by normal cellular metabolism.
[ "38", "33", "38" ]
79
11,643
0
false
oxidative and alkylation lesions commonly caused by normal cellular metabolism.
[]
oxidative and alkylation lesions commonly caused by normal cellular metabolism.
false
true
true
true
false
1,865
5
DISCUSSION
1
33
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
Induced mutagenesis data also support a role for FA proteins in promoting replication past a variety of DNA lesions, as the fancg cells have decreased recovery of hprt mutants after exposure to various DNA damaging agents, including UV-C, Ξ³-rays and ethylnitrosourea, relative to the parental control cells (33).
[ "38", "33", "38" ]
312
11,644
1
false
Induced mutagenesis data also support a role for FA proteins in promoting replication past a variety of DNA lesions, as the fancg cells have decreased recovery of hprt mutants after exposure to various DNA damaging agents, including UV-C, Ξ³-rays and ethylnitrosourea, relative to the parental control cells.
[ "33" ]
Induced mutagenesis data also support a role for FA proteins in promoting replication past a variety of DNA lesions, as the fancg cells have decreased recovery of hprt mutants after exposure to various DNA damaging agents, including UV-C, Ξ³-rays and ethylnitrosourea, relative to the parental control cells.
true
true
true
true
true
1,865
5
DISCUSSION
1
38
[ "B38", "B33", "B38" ]
17,517,774
pmid-15533833|NA|pmid-15533833
The unusually high sensitivity of fancg cells (38) (and FA cells generally) to crosslinking agents may be explained by the unique, dual requirement for TLS and HRR to bring about repair of broken replication forks resulting from cross-link processing.
[ "38", "33", "38" ]
251
11,645
1
false
The unusually high sensitivity of fancg cells (and FA cells generally) to crosslinking agents may be explained by the unique, dual requirement for TLS and HRR to bring about repair of broken replication forks resulting from cross-link processing.
[ "38" ]
The unusually high sensitivity of fancg cells (and FA cells generally) to crosslinking agents may be explained by the unique, dual requirement for TLS and HRR to bring about repair of broken replication forks resulting from cross-link processing.
true
true
true
true
true
1,865
6
DISCUSSION
1
33
[ "B33", "B33" ]
17,517,774
NA|NA
In summary, our gene amplification and hprt mutation studies emphasize both similarities and marked differences in phenotype between the FA and HRR mutants in an isogenic mammalian system.
[ "33", "33" ]
188
11,646
0
false
In summary, our gene amplification and hprt mutation studies emphasize both similarities and marked differences in phenotype between the FA and HRR mutants in an isogenic mammalian system.
[]
In summary, our gene amplification and hprt mutation studies emphasize both similarities and marked differences in phenotype between the FA and HRR mutants in an isogenic mammalian system.
true
true
true
true
true
1,866
6
DISCUSSION
1
33
[ "B33", "B33" ]
17,517,774
NA|NA
Our data combined with that in the literature support a model in which FANCD2 monoubiquitination acts upstream of TLS, HRR and NHEJ by supporting all three processes during S phase in response to endogenous and exogenous DNA damage (Figure 3).
[ "33", "33" ]
243
11,647
0
false
Our data combined with that in the literature support a model in which FANCD2 monoubiquitination acts upstream of TLS, HRR and NHEJ by supporting all three processes during S phase in response to endogenous and exogenous DNA damage (Figure 3).
[]
Our data combined with that in the literature support a model in which FANCD2 monoubiquitination acts upstream of TLS, HRR and NHEJ by supporting all three processes during S phase in response to endogenous and exogenous DNA damage.
true
true
true
true
true
1,866
6
DISCUSSION
1
33
[ "B33", "B33" ]
17,517,774
NA|NA
Although endogenous inter-strand crosslinks may contribute to the FA phenotype, our induced mutagenesis and survival studies argue that the FANC pathway is more globally important for diverse lesions (33).
[ "33", "33" ]
205
11,648
1
false
Although endogenous inter-strand crosslinks may contribute to the FA phenotype, our induced mutagenesis and survival studies argue that the FANC pathway is more globally important for diverse lesions.
[ "33" ]
Although endogenous inter-strand crosslinks may contribute to the FA phenotype, our induced mutagenesis and survival studies argue that the FANC pathway is more globally important for diverse lesions.
true
true
true
true
true
1,866
6
DISCUSSION
1
33
[ "B33", "B33" ]
17,517,774
NA|NA
We conclude that pathway coordination by FA proteins supports a β€˜Fire Captain’ model (33), in which they act to limit the severity of mutagenesis by promoting efficient TLS, HRR and NHEJ.
[ "33", "33" ]
187
11,649
1
false
We conclude that pathway coordination by FA proteins supports a β€˜Fire Captain’ model, in which they act to limit the severity of mutagenesis by promoting efficient TLS, HRR and NHEJ.
[ "33" ]
We conclude that pathway coordination by FA proteins supports a β€˜Fire Captain’ model, in which they act to limit the severity of mutagenesis by promoting efficient TLS, HRR and NHEJ.
true
true
true
true
true
1,866
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
RNA pseudoknots play an important role in many biological processes.
[ "1", "2", "3", "4" ]
68
11,650
0
false
RNA pseudoknots play an important role in many biological processes.
[]
RNA pseudoknots play an important role in many biological processes.
true
true
true
true
true
1,867
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
They build the catalytic core of some ribozymes (1,2) and are an important building block of many structural RNAs.
[ "1", "2", "3", "4" ]
114
11,651
0
false
They build the catalytic core of some ribozymes and are an important building block of many structural RNAs.
[ "1,2" ]
They build the catalytic core of some ribozymes and are an important building block of many structural RNAs.
true
true
true
true
true
1,867
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
Pseudoknots are involved in telomerase activity (3) and they stimulate efficient programmed -1 ribosomal frameshifting (-1 PRF), a mechanism used by a wide range of RNA viruses to encode two proteins within one genomic region.
[ "1", "2", "3", "4" ]
226
11,652
1
false
Pseudoknots are involved in telomerase activity and they stimulate efficient programmed -1 ribosomal frameshifting, a mechanism used by a wide range of RNA viruses to encode two proteins within one genomic region.
[ "3", "-1 PRF" ]
Pseudoknots are involved in telomerase activity and they stimulate efficient programmed -1 ribosomal frameshifting, a mechanism used by a wide range of RNA viruses to encode two proteins within one genomic region.
true
true
true
true
true
1,867
0
INTRODUCTION
1
4
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
In a recent study (4) over a thousand of potential -1 PRF signals were detected in the yeast genome.
[ "1", "2", "3", "4" ]
100
11,653
1
false
In a recent study over a thousand of potential -1 PRF signals were detected in the yeast genome.
[ "4" ]
In a recent study over a thousand of potential -1 PRF signals were detected in the yeast genome.
true
true
true
true
true
1,867
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
The majority of signals however seem to direct the ribosome to premature termination codons.
[ "1", "2", "3", "4" ]
92
11,654
0
false
The majority of signals however seem to direct the ribosome to premature termination codons.
[]
The majority of signals however seem to direct the ribosome to premature termination codons.
true
true
true
true
true
1,867
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
This suggests a mechanism of post-transcriptional gene regulation through the nonsense-mediated mRNA decay pathway.
[ "1", "2", "3", "4" ]
115
11,655
0
false
This suggests a mechanism of post-transcriptional gene regulation through the nonsense-mediated mRNA decay pathway.
[]
This suggests a mechanism of post-transcriptional gene regulation through the nonsense-mediated mRNA decay pathway.
true
true
true
true
true
1,867
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
Further genome wide studies have to elucidate this phenomenon.
[ "1", "2", "3", "4" ]
62
11,656
0
false
Further genome wide studies have to elucidate this phenomenon.
[]
Further genome wide studies have to elucidate this phenomenon.
true
true
true
true
true
1,867
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4" ]
17,478,505
pmid-9783582|pmid-12110898|pmid-15749017|pmid-17158156
This and many more applications require fast RNA folding algorithms, that are also capable of folding pseudoknots.
[ "1", "2", "3", "4" ]
114
11,657
0
false
This and many more applications require fast RNA folding algorithms, that are also capable of folding pseudoknots.
[]
This and many more applications require fast RNA folding algorithms, that are also capable of folding pseudoknots.
true
true
true
true
true
1,867
1
INTRODUCTION
1
5
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
Standard RNA folding programs (5,6) neglect pseudoknots for reasons of efficiency.
[ "5", "6", "7", "8" ]
82
11,658
0
false
Standard RNA folding programs neglect pseudoknots for reasons of efficiency.
[ "5,6" ]
Standard RNA folding programs neglect pseudoknots for reasons of efficiency.
true
true
true
true
true
1,868
1
INTRODUCTION
1
5
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
While the standard methods need time proportional to the cube of the input sequence length, pseudoknot prediction is much more demanding.
[ "5", "6", "7", "8" ]
137
11,659
0
false
While the standard methods need time proportional to the cube of the input sequence length, pseudoknot prediction is much more demanding.
[]
While the standard methods need time proportional to the cube of the input sequence length, pseudoknot prediction is much more demanding.
true
true
true
true
true
1,868
1
INTRODUCTION
1
5
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
This issue has attracted a large body of bio-informatics work, where all approaches either abandon the model of free energy minimization, or make restrictions on the class of pseudoknots that can be recognized.
[ "5", "6", "7", "8" ]
210
11,660
0
false
This issue has attracted a large body of bio-informatics work, where all approaches either abandon the model of free energy minimization, or make restrictions on the class of pseudoknots that can be recognized.
[]
This issue has attracted a large body of bio-informatics work, where all approaches either abandon the model of free energy minimization, or make restrictions on the class of pseudoknots that can be recognized.
true
true
true
true
true
1,868
1
INTRODUCTION
1
7
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
The well-known algorithm by Rivas and Eddy (7), which is able to predict a restricted class of pseudoknots, needs O(n6) time and O(n4) memory space, where n is the sequence length.
[ "5", "6", "7", "8" ]
180
11,661
1
false
The well-known algorithm by Rivas and Eddy, which is able to predict a restricted class of pseudoknots, needs O time and O(n4) memory space, where n is the sequence length.
[ "7", "n6" ]
The well-known algorithm by Rivas and Eddy, which is able to predict a restricted class of pseudoknots, needs O time and O(n4) memory space, where n is the sequence length.
true
true
true
true
true
1,868
1
INTRODUCTION
1
8
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
Even more restrictive, but more efficient by two orders of magnitude is the program pknotsRG by Reeder and Giegerich (8), requiring O(n4) time and O(n2) space.
[ "5", "6", "7", "8" ]
159
11,662
1
false
Even more restrictive, but more efficient by two orders of magnitude is the program pknotsRG by Reeder and Giegerich, requiring O(n4) time and O(n2) space.
[ "8" ]
Even more restrictive, but more efficient by two orders of magnitude is the program pknotsRG by Reeder and Giegerich, requiring O(n4) time and O(n2) space.
true
true
true
true
true
1,868
1
INTRODUCTION
1
5
[ "B5", "B6", "B7", "B8" ]
17,478,505
pmid-10329189|NA|pmid-9925784|pmid-15294028
The new method presented here re-implements and extends this approach in several significant ways.
[ "5", "6", "7", "8" ]
98
11,663
0
false
The new method presented here re-implements and extends this approach in several significant ways.
[]
The new method presented here re-implements and extends this approach in several significant ways.
true
true
true
true
true
1,868
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
The core replication machineries of Eukarya and Archaea are fundamentally related, indicative of their descent from a common ancestor.
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
134
11,664
0
false
The core replication machineries of Eukarya and Archaea are fundamentally related, indicative of their descent from a common ancestor.
[]
The core replication machineries of Eukarya and Archaea are fundamentally related, indicative of their descent from a common ancestor.
true
true
true
true
true
1,869
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Given the relative simplicity of the archaeal machinery, it serves as a valuable model system for dissection of the shared archaeo-eukaryotic replication machinery (1,2).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
170
11,665
0
false
Given the relative simplicity of the archaeal machinery, it serves as a valuable model system for dissection of the shared archaeo-eukaryotic replication machinery.
[ "1,2" ]
Given the relative simplicity of the archaeal machinery, it serves as a valuable model system for dissection of the shared archaeo-eukaryotic replication machinery.
true
true
true
true
true
1,869
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
The archaeal MCM is a homo-multimeric protein, while the MCM complex found in all eukarya is a heterohexamer composed of one copy of each of MCM 2, 3, 4, 5, 6 and 7.
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
165
11,666
0
false
The archaeal MCM is a homo-multimeric protein, while the MCM complex found in all eukarya is a heterohexamer composed of one copy of each of MCM 2, 3, 4, 5, 6 and 7.
[]
The archaeal MCM is a homo-multimeric protein, while the MCM complex found in all eukarya is a heterohexamer composed of one copy of each of MCM 2, 3, 4, 5, 6 and 7.
true
true
true
true
true
1,869
0
INTRODUCTION
1
3
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
MCM 2-7 display considerable sequence homology to each other, and are presumably derived by gene duplication events from a single, archaeal-like, ancestral MCM (3).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
164
11,667
1
false
MCM 2-7 display considerable sequence homology to each other, and are presumably derived by gene duplication events from a single, archaeal-like, ancestral MCM.
[ "3" ]
MCM 2-7 display considerable sequence homology to each other, and are presumably derived by gene duplication events from a single, archaeal-like, ancestral MCM.
true
true
true
true
true
1,869
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
In addition to MCM 2-7, recent work has described and characterised MCM 8, a homo-multimeric complex found exclusively in higher eukaryotes (4,5).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
146
11,668
0
false
In addition to MCM 2-7, recent work has described and characterised MCM 8, a homo-multimeric complex found exclusively in higher eukaryotes.
[ "4,5" ]
In addition to MCM 2-7, recent work has described and characterised MCM 8, a homo-multimeric complex found exclusively in higher eukaryotes.
true
true
true
true
true
1,869
0
INTRODUCTION
1
1
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
MCM 8 plays an important role in the elongation phase of replication, while MCM 2-7 is required for both initiation and elongation phases (5,6).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
144
11,669
0
false
MCM 8 plays an important role in the elongation phase of replication, while MCM 2-7 is required for both initiation and elongation phases.
[ "5,6" ]
MCM 8 plays an important role in the elongation phase of replication, while MCM 2-7 is required for both initiation and elongation phases.
true
true
true
true
true
1,869
0
INTRODUCTION
1
7
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
It is believed that MCM 2-7 serves as the replicative helicase and, in support of this, a sub-complex of MCM 4,6 and 7, but not the entire MCM 2-7 complex, possesses 3β€² to 5β€² helicase activity in vitro (7).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
206
11,670
1
false
It is believed that MCM 2-7 serves as the replicative helicase and, in support of this, a sub-complex of MCM 4,6 and 7, but not the entire MCM 2-7 complex, possesses 3β€² to 5β€² helicase activity in vitro.
[ "7" ]
It is believed that MCM 2-7 serves as the replicative helicase and, in support of this, a sub-complex of MCM 4,6 and 7, but not the entire MCM 2-7 complex, possesses 3β€² to 5β€² helicase activity in vitro.
true
true
true
true
true
1,869
0
INTRODUCTION
1
8–11
[ "B1", "B2", "B3", "B4", "B5", "B5", "B6", "B7", "B8 B9 B10 B11" ]
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Similarly, a number of archaeal MCMs have been demonstrated to have processive 3β€²-5β€² helicase activity (8–11).
[ "1", "2", "3", "4", "5", "5", "6", "7", "8–11" ]
110
11,671
1
false
Similarly, a number of archaeal MCMs have been demonstrated to have processive 3β€²-5β€² helicase activity.
[ "8–11" ]
Similarly, a number of archaeal MCMs have been demonstrated to have processive 3β€²-5β€² helicase activity.
true
true
true
true
true
1,869
1
INTRODUCTION
1
8
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
Electron microscopy has revealed that the MCM from the archaeon M. thermautotrophicum (Mth) can adopt a number of configurations, with hexamer, double hexamer, heptamer and filamentous structures observed (8,12–14).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
215
11,672
0
false
Electron microscopy has revealed that the MCM from the archaeon M. thermautotrophicum (Mth) can adopt a number of configurations, with hexamer, double hexamer, heptamer and filamentous structures observed.
[ "8,12–14" ]
Electron microscopy has revealed that the MCM from the archaeon M. thermautotrophicum (Mth) can adopt a number of configurations, with hexamer, double hexamer, heptamer and filamentous structures observed.
true
true
true
true
true
1,870
1
INTRODUCTION
1
8–10
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
In solution, Mth MCM appears to exist primarily as a double hexamer (8–10).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
75
11,673
1
false
In solution, Mth MCM appears to exist primarily as a double hexamer.
[ "8–10" ]
In solution, Mth MCM appears to exist primarily as a double hexamer.
true
true
true
true
true
1,870
1
INTRODUCTION
1
8
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
In contrast, studies to date indicate that the MCMs from Archaeoglobus fulgidus and Sulfolobus solfataricus (Sso) appear to be hexameric in solution (11,15).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
157
11,674
0
false
In contrast, studies to date indicate that the MCMs from Archaeoglobus fulgidus and Sulfolobus solfataricus (Sso) appear to be hexameric in solution.
[ "11,15" ]
In contrast, studies to date indicate that the MCMs from Archaeoglobus fulgidus and Sulfolobus solfataricus (Sso) appear to be hexameric in solution.
true
true
true
true
true
1,870
1
INTRODUCTION
1
15
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
Further, a hexameric form of Sso MCM has been shown to bind model DNA substrates (15).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
86
11,675
1
false
Further, a hexameric form of Sso MCM has been shown to bind model DNA substrates.
[ "15" ]
Further, a hexameric form of Sso MCM has been shown to bind model DNA substrates.
true
true
true
true
true
1,870
1
INTRODUCTION
1
16
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
The double hexameric nature of Mth MCM in solution has been supported by the X-ray crystal structure of the N-terminal 286 amino acids of the protein (16).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
155
11,676
1
false
The double hexameric nature of Mth MCM in solution has been supported by the X-ray crystal structure of the N-terminal 286 amino acids of the protein.
[ "16" ]
The double hexameric nature of Mth MCM in solution has been supported by the X-ray crystal structure of the N-terminal 286 amino acids of the protein.
true
true
true
true
true
1,870
1
INTRODUCTION
1
8
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
The structure revealed a sixfold symmetric arrangement, with hexameric rings forming double hexamers via a head-to-head interaction.
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
132
11,677
0
false
The structure revealed a sixfold symmetric arrangement, with hexameric rings forming double hexamers via a head-to-head interaction.
[]
The structure revealed a sixfold symmetric arrangement, with hexameric rings forming double hexamers via a head-to-head interaction.
true
true
true
true
true
1,870
1
INTRODUCTION
1
8
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
A zinc-binding motif in the N-terminus of each subunit was positioned at the site of interaction between hexamers, suggesting an important role for this motif in mediating double hexamerisation.
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
194
11,678
0
false
A zinc-binding motif in the N-terminus of each subunit was positioned at the site of interaction between hexamers, suggesting an important role for this motif in mediating double hexamerisation.
[]
A zinc-binding motif in the N-terminus of each subunit was positioned at the site of interaction between hexamers, suggesting an important role for this motif in mediating double hexamerisation.
true
true
true
true
true
1,870
1
INTRODUCTION
1
17
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
Intriguingly, however, mutational analysis of this motif did not reveal any alteration to multimeric status, but did show reduced DNA binding and helicase activity (17).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
169
11,679
1
false
Intriguingly, however, mutational analysis of this motif did not reveal any alteration to multimeric status, but did show reduced DNA binding and helicase activity.
[ "17" ]
Intriguingly, however, mutational analysis of this motif did not reveal any alteration to multimeric status, but did show reduced DNA binding and helicase activity.
true
true
true
true
true
1,870
1
INTRODUCTION
1
16
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
The structure of Mth MCM (2-286) revealed three domains, A, B and C (16).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
73
11,680
1
false
The structure of Mth MCM revealed three domains, A, B and C.
[ "2-286", "16" ]
The structure of Mth MCM revealed three domains, A, B and C.
true
true
true
true
true
1,870
1
INTRODUCTION
1
18
[ "B8", "B12 B13 B14", "B8 B9 B10", "B11", "B15", "B15", "B16", "B17", "B16", "B18" ]
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
Only domain C is essential for activity of Mth MCM and forms the core fold mediating multimerisation of the N-terminal portion of Mth MCM (18).
[ "8", "12–14", "8–10", "11", "15", "15", "16", "17", "16", "18" ]
143
11,681
1
false
Only domain C is essential for activity of Mth MCM and forms the core fold mediating multimerisation of the N-terminal portion of Mth MCM.
[ "18" ]
Only domain C is essential for activity of Mth MCM and forms the core fold mediating multimerisation of the N-terminal portion of Mth MCM.
true
true
true
true
true
1,870
2
INTRODUCTION
0
null
null
17,259,218
null
Here, we present an analysis of the Sso MCM and reveal that the C-terminal AAA+ domain, although dimeric in solution, retains helicase activity.
null
144
11,682
0
false
null
null
Here, we present an analysis of the Sso MCM and reveal that the C-terminal AAA+ domain, although dimeric in solution, retains helicase activity.
true
true
true
true
true
1,871
2
INTRODUCTION
0
null
null
17,259,218
null
The isolated AAA+ domain has promiscuous helicase activity, being able to catalyse melting of a broader range of model substrates than the full-length enzyme, including pure duplex and 5β€² tailed molecules.
null
205
11,683
0
false
null
null
The isolated AAA+ domain has promiscuous helicase activity, being able to catalyse melting of a broader range of model substrates than the full-length enzyme, including pure duplex and 5β€² tailed molecules.
true
true
true
true
true
1,871
2
INTRODUCTION
0
null
null
17,259,218
null
This promiscuity can be alleviated by addition of isolated N-terminal domains in trans.
null
87
11,684
0
false
null
null
This promiscuity can be alleviated by addition of isolated N-terminal domains in trans.
true
true
true
true
true
1,871
2
INTRODUCTION
0
null
null
17,259,218
null
In addition to modulating substrate specificity, the N-terminal domains, when added in trans, enhance the processivity of the enzyme.
null
133
11,685
0
false
null
null
In addition to modulating substrate specificity, the N-terminal domains, when added in trans, enhance the processivity of the enzyme.
true
true
true
true
true
1,871
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Our data reveal the functional modules that make up the Sso MCM and the complex net of interactions linking them (Figure 8).
null
124
11,686
0
false
null
null
Our data reveal the functional modules that make up the Sso MCM and the complex net of interactions linking them (Figure 8).
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
We have defined the AAA+ module as the minimal domain required for both helicase and ATPase activities.
null
103
11,687
0
false
null
null
We have defined the AAA+ module as the minimal domain required for both helicase and ATPase activities.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Previous studies using the Mth MCM were unable to test this directly due to an inability to express this domain in isolation.
null
125
11,688
0
false
null
null
Previous studies using the Mth MCM were unable to test this directly due to an inability to express this domain in isolation.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Our gel filtration and glutaraldehyde crosslinking data indicate that the AAA+ domain is capable of forming a range of multimeric forms.
null
136
11,689
0
false
null
null
Our gel filtration and glutaraldehyde crosslinking data indicate that the AAA+ domain is capable of forming a range of multimeric forms.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
The helicase activity of the isolated AAA+ domain suggests that it is capable of forming the active hexameric complex in the presence of substrate.
null
147
11,690
0
false
null
null
The helicase activity of the isolated AAA+ domain suggests that it is capable of forming the active hexameric complex in the presence of substrate.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
This may be similar to the situation found in other AAA+ family members that only achieve their full oligomeric status in the presence of their target.
null
151
11,691
0
false
null
null
This may be similar to the situation found in other AAA+ family members that only achieve their full oligomeric status in the presence of their target.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
Figure 8.Summary of interactions detected within the MCM complex.
null
65
11,692
0
false
null
null
Figure 8.Summary of interactions detected within the MCM complex.
true
true
true
true
true
1,872
0
DISCUSSION
0
null
null
17,259,218
NA|pmid-16467299|NA|pmid-12771218|pmid-15707891|pmid-15707891|NA|pmid-9305914|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732
The dotted lines indicate that the N-half-core interactions could be occurring in cis and/or trans.
null
99
11,693
0
false
null
null
The dotted lines indicate that the N-half-core interactions could be occurring in cis and/or trans.
true
true
true
true
true
1,872
1
DISCUSSION
0
null
null
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
Summary of interactions detected within the MCM complex.
null
56
11,694
0
false
null
null
Summary of interactions detected within the MCM complex.
true
true
true
true
true
1,873
1
DISCUSSION
0
null
null
17,259,218
pmid-10677495|pmid-15670590|pmid-12151340|pmid-14566326|pmid-10677495|pmid-10611290|pmid-10747908|pmid-12907732|pmid-16116441|pmid-16116441|pmid-12548282|pmid-11606589|pmid-12548282|pmid-15100218
The dotted lines indicate that the N-half-core interactions could be occurring in cis and/or trans.
null
99
11,695
0
false
null
null
The dotted lines indicate that the N-half-core interactions could be occurring in cis and/or trans.
true
true
true
true
true
1,873
2
DISCUSSION
0
null
null
17,259,218
null
The presence of the N-half, although not essential, is clearly stimulatory to the 3β€² end dependent helicase activity of the AAA+ domain.
null
136
11,696
0
false
null
null
The presence of the N-half, although not essential, is clearly stimulatory to the 3β€² end dependent helicase activity of the AAA+ domain.
true
true
true
true
true
1,874
2
DISCUSSION
0
null
null
17,259,218
null
This is evident either when the domains are covalently joined or mixed together as isolated fragments.
null
102
11,697
0
false
null
null
This is evident either when the domains are covalently joined or mixed together as isolated fragments.
true
true
true
true
true
1,874
2
DISCUSSION
0
null
null
17,259,218
null
Previously, the highly stable double hexameric nature of the N-terminal half of Mth MCM had implicated it as the organising centre of the complex.
null
146
11,698
0
false
null
null
Previously, the highly stable double hexameric nature of the N-terminal half of Mth MCM had implicated it as the organising centre of the complex.
true
true
true
true
true
1,874
2
DISCUSSION
0
null
null
17,259,218
null
However, we find that the exactly analogous region of Sso MCM forms a range of lower-order multimeric forms in solution, suggesting that the stable formation of a double hexamer is not key to the role of the N-half in SsoMCM.
null
225
11,699
0
false
null
null
However, we find that the exactly analogous region of Sso MCM forms a range of lower-order multimeric forms in solution, suggesting that the stable formation of a double hexamer is not key to the role of the N-half in SsoMCM.
true
true
true
true
true
1,874