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1 ric mutator variant of DNA polymerase delta (Pol delta).
2 B and identified it as DNA polymerase delta (Pol delta).
3 DL but does not affect primer recognition by Pol delta.
4 ry subunit of the replicative DNA polymerase Pol delta.
5 nal mismatches to enable primer extension by Pol delta.
6 s PCNA at the DNA nick generated by FEN1 and Pol delta.
7 s with accessory subunits of replicative DNA Pol delta.
8 n cellular DNA replication than depletion of Pol delta.
9 properties in comparison with Pol alpha and Pol delta.
10 es the rate and fidelity of DNA synthesis by Pol delta.
11 ogous mutations at position Leu-606 in human pol delta.
12 ady state kinetic studies of the fidelity of pol delta.
13 on by the active site than that of wild type pol delta.
14 n are distinct from the errors made by human Pol delta.
15 nd processivity similar to that of wild type pol delta.
16 than for those same mismatches when made by Pol delta.
17 d recombinagenic responses to the failure of Pol delta.
18 prevented by the 3.-exonuclease activity of Pol delta.
19 t implicates PP1 in the dephosphorylation of Pol delta.
20 ved motif A in the polymerase active site of Pol delta.
21 spectrum characteristic of mistakes made by Pol delta.
22 fidelity of DNA synthesis in vitro by yeast pol delta.
23 condary UV irradiation, and DNA synthesis by Pol delta.
24 of the rate and fidelity of DNA synthesis by pol delta.
25 shared with the replicative DNA polymerase, pol delta.
26 MMEJ substrates following DSB induction than Pol delta.
32 zyme, suggesting that CMG may bind and alter Pol delta activity or position it on the lagging strand.
33 icate that p12 contributes to PCNA-dependent pol delta activity, i.e. the p12-PCNA interaction is fun
34 ain the regulation of the oxidation state on Pol delta activity, possibly useful during cellular oxid
36 s in Saccharomyces cerevisiae using a mutant Pol delta allele (pol3-L612M) whose error rate is higher
37 ase errors are similar to those generated by pol delta alone, indicating that pol delta itself is by
43 and LigI remain on the DNA, indicating that Pol delta and FEN1 dissociate during 5' end processing a
45 Here we describe a novel interaction between Pol delta and LigI that is critical for Okazaki fragment
47 the hypothesis that the interaction between pol delta and PCNA is a divalent one that involves p12 a
51 ubstitution of the high-fidelity replicative pol delta and pol epsilon with the TLS pol theta, pol et
55 locking lesions occur by the exchange of the Pol delta and Pol zeta catalytic subunits on a preassemb
56 conserved and similar C-terminal domains of Pol delta and Pol zeta contain a [4Fe-4S] cluster coordi
58 though high-fidelity DNA polymerases such as pol delta and the bacteriophage T4 DNA polymerase replic
64 H2, Ku, DNA-PKcs, MCM proteins, PCNA and DNA Pol delta) and in protein metabolic processes, including
65 primer and extended by DNA polymerase delta (pol delta) and the replication clamp proliferating cell
67 at takes place in both DNA polymerase delta (Pol delta)- and DNA polymerase (Pol )-dependent MMR reac
68 yeast Pol eta is 10-fold more efficient than Pol delta, and following bypass Pol eta switches to less
70 erases alpha, delta, and epsilon (Pol alpha, Pol delta, and Pol epsilon), are responsible for eukaryo
71 three replicative DNA polymerases Pol alpha, Pol delta, and Pol epsilon; and canonical maturation of
72 ivity of proliferating cell nuclear antigen, Pol-delta, and Pol-epsilon, and it contributes to the ph
75 ken together, the changes that p12 exerts on Pol delta are ones that can modulate its fidelity of DNA
76 ts, deficient in the exonuclease activity of Pol delta are partially deficient in the repair of these
77 lon as the leading strand DNA polymerase and Pol delta as the lagging strand polymerase during undist
79 its of the replicative DNA polymerase delta (Pol delta) as promoters of Alt-NHEJ that results in more
82 ced telomere synthesis requires the RFC-PCNA-Pol delta axis, but is independent of other canonical re
86 isingly, the main lagging-strand polymerase, Pol delta, binds the leading strand upon uncoupling and
89 imulates the strand displacement activity of Pol delta but it also allows efficient replication throu
91 m the fork progression, or by recruitment of Pol delta, but not Pol epsilon, to post-replicative proc
94 ults demonstrate that the [4Fe4S] cluster in Pol delta can act as a redox switch for activity, and we
95 hat Pol alpha-primase and the lagging-strand Pol delta can be re-used within the replisome to support
99 wer CMG, and in the absence of a stabilizing Pol delta-CMG interaction, the collision release process
100 nucleotide incorporation by a preformed DNA-Pol delta complex in the absence of PCNA was 40 s-1.
102 due to strand invasion failure, whereas the Pol delta complex mutants are proficient for strand inva
106 In addition to its catalytic subunit (p125), pol delta comprises three regulatory subunits (p50, p68,
108 ivities and reaction products of recombinant pol delta containing a p12 mutant defective in PCNA bind
113 alysis of DNA synthesis progression by human Pol delta demonstrated significant synthesis perturbatio
115 e extent of strand displacement synthesis by Pol delta determines whether maturation proceeds by the
116 e proposed pathway for flap removal involves pol delta displacement of long flaps, coating of those f
117 howed that in the presence of PCNA and FEN1, pol delta displacement synthesis favors formation and cl
118 Primer extension by DNA polymerase delta (pol delta) displaces the downstream fragment into an RNA
120 This approach identifies DNA pol alpha, DNA pol delta, DNA pol varepsilon, MCM2-7, Cdc45, GINS, and
121 on cryo-EM structure of the human processive Pol delta-DNA-PCNA complex in the absence and presence o
128 ex' lesions, demonstrating the importance of Pol delta during the repair of DNA lesions in close prox
129 ed by a "collision release" process in which pol delta ejects from PCNA upon extending a DNA template
130 GMP or A-dCMP for T to C transitions), L612M pol delta error rates are substantially higher for one m
131 the basic biochemical properties that allow Pol delta-exo(-) to carry out strand displacement synthe
135 human specialized Pols from three families: Pol delta (family B), Pol eta and Pol iota (family Y), a
139 n of the activities of DNA polymerase delta (Pol delta), flap endonuclease 1 (FEN1) and DNA ligase I
140 racts with the enzymes DNA polymerase delta (Pol delta), flap endonuclease 1 (FEN1) and DNA ligase I
142 eta binds to the Pol31 and Pol32 subunits of Pol delta, forming a four-subunit Pol zeta(4) complex (R
144 f this conclusion, we show that depletion of Pol delta from cells reduces BIR, whereas depletion of P
148 polymerase in eukaryotes, polymerase delta (pol delta), functions with the proliferating cell nuclea
149 Compared with wild type pol delta, L612M pol delta has normal processivity and slightly higher po
151 cerevisae where the extreme stability of the pol delta holoenzyme ensures that every nucleobase withi
154 characteristic of the human DNA polymerase (Pol delta) holoenzyme (150 bp for one binding event), co
155 function of the human DNA polymerase delta (Pol delta) holoenzyme by comparing the kinetics of DNA s
156 inct from that of L868M/F Pol alpha or L612M Pol delta, implying that each polymerase has different a
157 eta, or eta, all of which are able to assist pol delta in 8-oxo-G bypass by translesion synthesis (TL
159 d DNA, but the activity was not shut down by Pol delta in accord with rapid association/dissociation
160 eavage products on flaps strand-displaced by pol delta in an oligonucleotide system reconstituted wit
162 the 3.2- angstrom cryo-EM structure of S.c. Pol delta in complex with primed DNA, an incoming ddTTP,
163 nuclease activity and its cooperativity with Pol delta in preserving genome stability, which is compr
164 l zeta extended the DL more efficiently than Pol delta in the absence of PCNA, but little or no stimu
165 NA binding affinities and stoichiometries by Pol delta in the absence of PCNA, using electrophoretic
167 s of recombinant human DNA polymerase delta (Pol delta) in which one or two of the three conserved As
171 elta (lagging strand polymerase) and Mgs1 (a pol delta interacting protein) lead to a defect in fusio
178 In this report, Saccharomyces cerevisiae pol delta is examined on model substrates to gain insigh
181 In vitro, the generation of short flaps by Pol delta is not affected by the presence of Pol32; howe
184 strand bias strongly supports the idea that Pol delta is primarily a lagging strand polymerase durin
189 veral types of repair, DNA polymerase delta (pol delta) is assisted by replication protein A (RPA), t
191 rtantly, we found that DNA polymerase delta (Pol delta) is critical for MMEJ, independent of microhom
197 Although Pol32 is an integral component of Pol delta, it is also required for translesion synthesis
198 enerated by pol delta alone, indicating that pol delta itself is by far the prime determinant of fide
200 nstrated that heterozygous expression of the pol delta L604G variant in mice results in normal life s
203 high frequency during DNA synthesis, whereas pol delta L606K is extremely accurate, with a higher fid
205 amino acid in yeast Pol alpha (L868M/F) and Pol delta (L612M), these data indicate that the active s
207 g mutants of DNA polymerases; defects in DNA pol delta (lagging strand polymerase) and Mgs1 (a pol de
209 urprisingly, the results indicate that human pol delta maintains a loose association with PCNA while
210 We suggest that reduction in the level of Pol delta may be less deleterious because of its collisi
212 post-replication act as partial barriers to Pol-delta-mediated displacement of Pol-alpha-synthesized
213 icate that the exonuclease activity of human Pol delta modulates its intrinsic bypass efficiency on t
215 showed substantially less stimulation of the Pol delta nucleotide incorporation rate, identifying the
219 s in humans as it limits the processivity of pol delta on undamaged DNA and promotes the rapid dissoc
221 that deletion of the POL32 (third subunit of Pol delta) or PIF1 helicase genes can suppress lethality
222 We also show that CK2 phosphorylates the Pol delta p125, p68, and p12 subunits and that these pho
225 Using DNA trap experiments, we show that Pol delta pauses within CFS sequences are sites of enzym
226 upon completing replication, and we propose Pol delta-PCNA collides with the slower CMG, and in the
227 could play a role in stabilizing the overall pol delta-PCNA complex as well as pol delta itself.
237 ogether, these data support a model in which Pol delta promotes Alt-NHEJ in human cells at DSBs, incl
238 mutator phenotype), and inactivation of both Pol delta proofreading (pol3-01) and MMR is lethal due t
241 hich causes defects in DNA polymerase delta (Pol delta) proofreading (pol3-01) and nucleotide selecti
242 ng the hypothesis that the 3' exonuclease of pol delta proofreads errors generated by pol alpha durin
243 nd PCNA are included in reactions containing pol delta, rates for single base errors are similar to t
248 d by hydrolytic end sequencing, we show that Pol delta replicates both the invading and the complemen
249 main of Pol3, suggesting that all aspects of Pol delta replication are important to human health and
251 on origin, in a manner implying that >90% of Pol delta replication is performed using the lagging str
252 t that, unlike its prokaryotic counterparts, pol delta requires replication accessory factors like pr
253 s of many of the amino acid substitutions in Pol delta resemble those of previously identified antimu
255 The corresponding mutation in purified human Pol delta results in a similar 30-fold increase in mutat
256 to-Gln substitution in the fingers domain of Pol delta results in an interaction with the N-terminal
257 ssays following electrochemical oxidation of Pol delta reveal a significant slowing of DNA synthesis
260 work sheds light on the structural basis of Pol delta's activity in replicating the human genome.
261 rinsic 3'-exonuclease activity, implies that Pol delta should have high base substitution fidelity.
263 sis, are observed when either Pol epsilon or Pol delta stalls at leading-strand damage, and do not re
264 tionally, a fold-back in the template slowed pol delta synthesis, so that the fragment could be remov
267 rystal structure of Saccharomyces cerevisiae Pol delta template reveals four potential contacts for A
268 NA-DNA hybrids are more readily displaced by Pol delta than DNA hybrids, thereby favoring degradation
270 ve for FEN1(RAD27) and the 3.-exonuclease of Pol delta) that produce long flaps and of dna2Delta muta
271 ated by two DNA polymerases, Pol epsilon and Pol delta, that function on the leading and lagging stra
273 e primer for the continuous DNA synthesis by pol delta, thereby leading to hairpin retention and repe
274 kappa was significantly more efficient than Pol delta through both types of repetitive elements.
276 on exposure to DNA-damaging agents, converts Pol delta to a form that has an increased capacity for p
277 of a single Rap1 molecule; Pif1 also allows Pol delta to carry out DNA synthesis across an array of
278 nt of Pol delta to the DL but stimulation of Pol delta to displace a DNA strand during DL extension.
281 t C:8-oxo-G can be overcome by a switch from pol delta to pols lambda, beta, or eta, all of which are
282 Here we investigate the contribution of Pol delta to replication of the leading and lagging stra
283 ial role of PCNA in HR is not recruitment of Pol delta to the DL but stimulation of Pol delta to disp
284 erating cell nuclear antigen (PCNA) recruits Pol delta to the DNA and serves as a processivity factor
287 expressing the error-prone but not wild-type Pol delta variant, which is not observed following treat
292 al errors generated by DNA polymerase delta (Pol delta), which takes over for Pol alpha to complete l
293 mical properties of Saccharomyces cerevisiae pol delta with a methionine replacing conserved leucine
296 placement synthesis by DNA polymerase delta (Pol delta) with 5.-flap cutting by FEN1(RAD27) endonucle
297 icases in human cells, DNA polymerase delta (Pol delta), with an error-prone variant allows increased
298 ded PCNA greatly stimulates DNA synthesis by Pol delta within the DL but does not affect primer recog
299 we provide evidence that PolDIP2 stimulates Pol delta without affecting its fidelity, facilitating t
300 present evidence that WRN can proofread for Pol delta; WRN excises 3'-terminal mismatches to enable