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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 ccharomyces cerevisiae DNA polymerase delta (Pol delta).
4 t associate with human DNA polymerase delta (pol delta).
5 nal mismatches to enable primer extension by Pol delta.
6 s with accessory subunits of replicative DNA Pol delta.
7 n cellular DNA replication than depletion of Pol delta.
8 properties in comparison with Pol alpha and Pol delta.
9 es the rate and fidelity of DNA synthesis by Pol delta.
10 ogous mutations at position Leu-606 in human pol delta.
11 ady state kinetic studies of the fidelity of pol delta.
12 on by the active site than that of wild type pol delta.
13 n are distinct from the errors made by human Pol delta.
14 nd processivity similar to that of wild type pol delta.
15 than for those same mismatches when made by Pol delta.
16 d recombinagenic responses to the failure of Pol delta.
17 prevented by the 3.-exonuclease activity of Pol delta.
18 t implicates PP1 in the dephosphorylation of Pol delta.
19 ved motif A in the polymerase active site of Pol delta.
20 fidelity of DNA synthesis in vitro by yeast pol delta.
21 raction with p50, the small subunit of human pol delta.
22 (612) in Motif A of Saccharomyces cerevisiae Pol delta.
23 normally expressed at low levels relative to pol delta.
24 studied exonuclease-defective mutants of the Pol delta.
25 cleotides inserted opposite these lesions by Pol delta.
26 MMEJ substrates following DSB induction than Pol delta.
27 DL but does not affect primer recognition by Pol delta.
28 ry subunit of the replicative DNA polymerase Pol delta.
33 zyme, suggesting that CMG may bind and alter Pol delta activity or position it on the lagging strand.
34 icate that p12 contributes to PCNA-dependent pol delta activity, i.e. the p12-PCNA interaction is fun
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
44 the hypothesis that the interaction between pol delta and PCNA is a divalent one that involves p12 a
49 ubstitution of the high-fidelity replicative pol delta and pol epsilon with the TLS pol theta, pol et
53 locking lesions occur by the exchange of the Pol delta and Pol zeta catalytic subunits on a preassemb
54 conserved and similar C-terminal domains of Pol delta and Pol zeta contain a [4Fe-4S] cluster coordi
56 though high-fidelity DNA polymerases such as pol delta and the bacteriophage T4 DNA polymerase replic
58 P38 to interact with both the p50 subunit of pol delta and with PCNA was confirmed by pull-down assay
63 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 -subunit pol alpha, the catalytic subunit of pol delta, and the Mcm467 complex each inhibited DNA syn
73 ivity of proliferating cell nuclear antigen, Pol-delta, and Pol-epsilon, and it contributes to the ph
76 ken together, the changes that p12 exerts on Pol delta are ones that can modulate its fidelity of DNA
77 ts, deficient in the exonuclease activity of Pol delta are partially deficient in the repair of these
78 teractions with POL31, the second subunit of Pol delta, are specified by the amino-terminal 92 amino
79 lon as the leading strand DNA polymerase and Pol delta as the lagging strand polymerase during undist
83 ced telomere synthesis requires the RFC-PCNA-Pol delta axis, but is independent of other canonical re
85 may be required for the efficient bypass of pol delta-blocking N2-G adducts bulkier than N2-EtG in h
86 synthesis by purified DNA polymerase delta (pol delta) both on unmodified templates and past chemica
88 imulates the strand displacement activity of Pol delta but it also allows efficient replication throu
90 m the fork progression, or by recruitment of Pol delta, but not Pol epsilon, to post-replicative proc
91 ism for Okazaki fragment maturation in which Pol delta by default displaces 2-3 nt of any downstream
94 ults demonstrate that the [4Fe4S] cluster in Pol delta can act as a redox switch for activity, and we
96 is study because the replicative polymerase, Pol delta, can replicate through them, albeit weakly.
98 wer CMG, and in the absence of a stabilizing Pol delta-CMG interaction, the collision release process
100 due to strand invasion failure, whereas the Pol delta complex mutants are proficient for strand inva
105 Measurements with exonuclease-deficient Pol delta confirm the high nucleotide selectivity of the
107 ivities and reaction products of recombinant pol delta containing a p12 mutant defective in PCNA bind
114 alysis of DNA synthesis progression by human Pol delta demonstrated significant synthesis perturbatio
116 e extent of strand displacement synthesis by Pol delta determines whether maturation proceeds by the
117 e proposed pathway for flap removal involves pol delta displacement of long flaps, coating of those f
118 howed that in the presence of PCNA and FEN1, pol delta displacement synthesis favors formation and cl
119 Primer extension by DNA polymerase delta (pol delta) displaces the downstream fragment into an RNA
121 This approach identifies DNA pol alpha, DNA pol delta, DNA pol varepsilon, MCM2-7, Cdc45, GINS, and
122 type Saccharomyces cerevisiae three-subunit Pol delta does indeed have high base substitution fideli
126 ex' lesions, demonstrating the importance of Pol delta during the repair of DNA lesions in close prox
127 ed by a "collision release" process in which pol delta ejects from PCNA upon extending a DNA template
128 GMP or A-dCMP for T to C transitions), L612M pol delta error rates are substantially higher for one m
129 the basic biochemical properties that allow Pol delta-exo(-) to carry out strand displacement synthe
134 human specialized Pols from three families: Pol delta (family B), Pol eta and Pol iota (family Y), a
137 n of the activities of DNA polymerase delta (Pol delta), flap endonuclease 1 (FEN1) and DNA ligase I
139 eta binds to the Pol31 and Pol32 subunits of Pol delta, forming a four-subunit Pol zeta(4) complex (R
144 polymerase in eukaryotes, polymerase delta (pol delta), functions with the proliferating cell nuclea
145 Compared with wild type pol delta, L612M pol delta has normal processivity and slightly higher po
148 cerevisae where the extreme stability of the pol delta holoenzyme ensures that every nucleobase withi
151 characteristic of the human DNA polymerase (Pol delta) holoenzyme (150 bp for one binding event), co
152 function of the human DNA polymerase delta (Pol delta) holoenzyme by comparing the kinetics of DNA s
153 inct from that of L868M/F Pol alpha or L612M Pol delta, implying that each polymerase has different a
154 eta, or eta, all of which are able to assist pol delta in 8-oxo-G bypass by translesion synthesis (TL
156 d DNA, but the activity was not shut down by Pol delta in accord with rapid association/dissociation
157 eavage products on flaps strand-displaced by pol delta in an oligonucleotide system reconstituted wit
159 nuclease activity and its cooperativity with Pol delta in preserving genome stability, which is compr
160 l zeta extended the DL more efficiently than Pol delta in the absence of PCNA, but little or no stimu
162 s of recombinant human DNA polymerase delta (Pol delta) in which one or two of the three conserved As
165 elta (lagging strand polymerase) and Mgs1 (a pol delta interacting protein) lead to a defect in fusio
172 ndividual dNTPs opposite a template guanine, Pol delta is believed to have high selectivity for inser
173 bypass of 8-oxoG and m6G lesions occurs when Pol delta is combined with Pol zeta, indicating a role f
174 In this report, Saccharomyces cerevisiae pol delta is examined on model substrates to gain insigh
177 n both have high base substitution fidelity, Pol delta is much less accurate than Pol epsilon for del
178 In vitro, the generation of short flaps by Pol delta is not affected by the presence of Pol32; howe
181 strand bias strongly supports the idea that Pol delta is primarily a lagging strand polymerase durin
186 veral types of repair, DNA polymerase delta (pol delta) is assisted by replication protein A (RPA), t
188 rtantly, we found that DNA polymerase delta (Pol delta) is critical for MMEJ, independent of microhom
194 Although Pol32 is an integral component of Pol delta, it is also required for translesion synthesis
195 enerated by pol delta alone, indicating that pol delta itself is by far the prime determinant of fide
197 nstrated that heterozygous expression of the pol delta L604G variant in mice results in normal life s
200 high frequency during DNA synthesis, whereas pol delta L606K is extremely accurate, with a higher fid
202 amino acid in yeast Pol alpha (L868M/F) and Pol delta (L612M), these data indicate that the active s
204 g mutants of DNA polymerases; defects in DNA pol delta (lagging strand polymerase) and Mgs1 (a pol de
206 reas interactions of the other subunit(s) of Pol delta localize largely to a hydrophobic pocket at th
207 urprisingly, the results indicate that human pol delta maintains a loose association with PCNA while
208 and slippage during replication by wild type Pol delta may be a primary source of insertion and delet
209 We suggest that reduction in the level of Pol delta may be less deleterious because of its collisi
210 e the possibility that it may be involved in pol delta-mediated DNA replication or DNA repair under c
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
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.
233 hese switches using Saccharomyces cerevisiae Pol delta, Pol epsilon and Pol eta and a series of match
240 mutator phenotype), and inactivation of both Pol delta proofreading (pol3-01) and MMR is lethal due t
243 hich causes defects in DNA polymerase delta (Pol delta) proofreading (pol3-01) and nucleotide selecti
244 ng the hypothesis that the 3' exonuclease of pol delta proofreads errors generated by pol alpha durin
245 nd PCNA are included in reactions containing pol delta, rates for single base errors are similar to t
246 was seen but depended both on the exact PCNA/pol delta ratio tested and on the specific nature of the
252 on origin, in a manner implying that >90% of Pol delta replication is performed using the lagging str
253 t that, unlike its prokaryotic counterparts, pol delta requires replication accessory factors like pr
254 s of many of the amino acid substitutions in Pol delta resemble those of previously identified antimu
256 The corresponding mutation in purified human Pol delta results in a similar 30-fold increase in mutat
257 to-Gln substitution in the fingers domain of Pol delta results in an interaction with the N-terminal
258 ssays following electrochemical oxidation of Pol delta reveal a significant slowing of DNA synthesis
261 rinsic 3'-exonuclease activity, implies that Pol delta should have high base substitution fidelity.
263 tionally, a fold-back in the template slowed pol delta synthesis, so that the fragment could be remov
266 rystal structure of Saccharomyces cerevisiae Pol delta template reveals four potential contacts for A
267 NA-DNA hybrids are more readily displaced by Pol delta than DNA hybrids, thereby favoring degradation
269 ve for FEN1(RAD27) and the 3.-exonuclease of Pol delta) that produce long flaps and of dna2Delta muta
270 ated by two DNA polymerases, Pol epsilon and Pol delta, that function on the leading and lagging stra
272 e primer for the continuous DNA synthesis by pol delta, thereby leading to hairpin retention and repe
273 kappa was significantly more efficient than Pol delta through both types of repetitive elements.
275 on exposure to DNA-damaging agents, converts Pol delta to a form that has an increased capacity for p
276 or not optimally functional, the ability of Pol delta to back up via its 3'-5'-exonuclease activity,
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
291 ' exonuclease of yeast DNA polymerase delta (Pol delta) we have discerned additional biological roles
293 al errors generated by DNA polymerase delta (Pol delta), which takes over for Pol alpha to complete l
294 mical properties of Saccharomyces cerevisiae pol delta with a methionine replacing conserved leucine
297 placement synthesis by DNA polymerase delta (Pol delta) with 5.-flap cutting by FEN1(RAD27) endonucle
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
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