ライフサイエンスコーパス: leading strand

1 lation of Pole-P301R-generated errors on the leading strand.

2 epair to the continuously replicated nascent leading strand.

3 ccessible 3'-OH group in the template of the leading strand.

4 ' efficiency than 'those that anneal to' the leading strand.

5 t with more common template switching on the leading strand.

6 as for fusion of telomeres replicated by the leading strand.

7 ff at the Top1 cleavage complex sites on the leading strand.

8 ase checkpoint response to DNA damage on the leading strand.

9 nt lagging strand at the branch point but no leading strand.

10 on forks where there is a gap in the nascent leading strand.

11 lizes fork structures with large gaps in the leading strand.

12 s, likely due to uncoupling from the stalled leading strand.

13 cess is triggered, ejecting Pol delta on the leading strand.

14 rand and CMG enforces quality control on the leading strand.

15 lta is slow and distributive with CMG on the leading strand.

16 lagging strand replication compared with the leading strand.

17 ts Pol epsilon against RFC inhibition on the leading strand.

18 ch higher rate when (TG)2 was on the nascent leading strand.

19 tially to a fork substrate with a gap in the leading strand.

20 rmediates come from both the lagging and the leading strands.

21 3/iCy5) chromophore pairs in the lagging and leading strands.

22 us DNA synthesis of both the lagging and the leading strands.

23 d DNA structures, and translocates along the leading strand (3' to 5' direction).

24 repair events nick continuously synthesized leading strands after synthesis, producing the observed

25 RR pathway when the lesion is located on the leading strand and a role for the Rad52 pathway when the

26 gle ribonucleotide at the 5' end of both the leading strand and at least the first Okazaki fragment i

27 ands that are extended by Pol epsilon on the leading strand and by Pol delta on the lagging strand.

28 CMG (Cdc45-MCM-GINS) helicase surrounds the leading strand and is proposed to recruit Pol epsilon fo

29 DNA replication, initiating synthesis of the leading strand and of each Okazaki fragment on the laggi

30 eukaryotic cells, Pol epsilon being the main leading strand and Pol delta the lagging strand DNA poly

31 for specific targeting of Pol epsilon to the leading strand and provides clear mechanistic evidence f

32 tinuous polymerization of nucleotides on the leading strand and the discontinuous synthesis of DNA on

33 r substrates that contain no gap between the leading strand and the duplex portion of the fork, as de

34 Their increased abundance on leading strands and decreased abundance on lagging stran

35 case binds Pol epsilon and tethers it to the leading strand, and PCNA (proliferating cell nuclear ant

36 jority of bacterial genes are located on the leading strand, and the percentage of such genes has a l

37 that translocate on the spirally-configured leading strand, and thereby pull the preceding DNA segme

38 ination, translesion replication (TR) on the leading strand, and TR on the lagging strand.

39 r replication forks collide with an ICL, the leading strand approaches to within one nucleotide of th

40 a model fork, than to the 3' single-stranded leading strand arm.

41 nd CMG helps to stabilize Pol epsilon on the leading strand as part of a 15-subunit leading-strand ho

42 NA polymerase epsilon, which synthesises the leading strand at DNA replication forks.

43 NA polymerase epsilon, which synthesizes the leading strand at replication forks and is an important

44 tes with the DNA polymerase that acts on the leading strand at replication forks, suggesting a potent

45 pair is to unhook the damage by incising the leading strand at the 3' side of an ICL lesion.

46 inding with primer synthesis to initiate the leading strand at the viral origin and each Okazaki frag

47 er-strand positive effect on the rate of the leading strand based in its interaction with the replica

48 coli postulates continuous synthesis of the leading strand, based on in vitro experiments with purif

49 is important for fitness are selected to the leading strand because this reduces the duration of thes

50 The leading strand bias was lost in the absence of exonuclea

51 central hole of the hexagonal helicase, the leading strand binds to the "outside" surfaces of subuni

52 Hence, Pol epsilon is active with CMG on the leading strand, but it is unable to function on the lagg

53 no-acid-changing mutations tend to be on the leading strand, co-oriented with replication.

54 more mismatches during replication than its leading-strand counterpart, polymerase epsilon; that mos

55 some is able to directly replicate through a leading-strand cyclobutane pyrimidine dimer (CPD) lesion

56 en either Pol epsilon or Pol delta stalls at leading-strand damage, and do not require specific helic

57 that the creation of a flap at the site of a leading strand discontinuity could, in principle, allow

58 ons without dissociating by synthesizing the leading strand discontinuously.

59 lling-circle mechanism that exclusively uses leading strand displacement synthesis.

60 The eukaryotic leading strand DNA polymerase (Pol) epsilon contains 4 s

61 ody of evidence specifies Pol epsilon as the leading strand DNA polymerase and Pol delta as the laggi

62 Unexpectedly, the leading strand DNA polymerase epsilon (Polepsilon) arriv

63 activation and support a model in which the leading strand DNA polymerase is recruited prior to orig

64 role after initiation, because it links the leading strand DNA polymerase to the Cdc45-MCM-GINS heli

65 llowing completion of DNA replication by the leading strand DNA polymerase, and associated histone mo

66 we show that mutational inactivation of the leading strand DNA polymerase, Pol epsilon, dNTP depleti

67 Finally, recruitment of lagging but not leading strand DNA polymerases depends on Mcm10 and DNA

68 RNA-DNA fragments for priming of lagging and leading strand DNA replication in eukaryotes.

69 agility and the first known role for FEN1 in leading strand DNA replication.

70 DNA polymerase (Pol) epsilon mediates leading strand DNA replication.

71 psilon (Pol epsilon) carries out the bulk of leading strand DNA synthesis at an undisturbed replicati

72 Leading strand DNA synthesis requires functional couplin

73 ying a major role in fork progression during leading strand DNA synthesis, we propose that TWINKLE is

74 omes showed loss of telomeres synthesized by leading strand DNA synthesis.

75 unwinding of the duplex prior to subsequent leading strand DNA synthesis.

76 cation proceeds with continuous synthesis of leading-strand DNA and discontinuous synthesis of laggin

77 referential for repair of mismatches made by leading-strand DNA polymerase epsilon as compared to lag

78 rmed because of stochastic uncoupling of the leading-strand DNA polymerase from the replication fork

79 hesis and to a surprising obstruction of the leading-strand DNA polymerase in vitro, pointing to role

80 , the replicative DNA helicase, MCM, and the leading-strand DNA polymerase, Pol epsilon, move beyond

81 nit of DNA polymerase epsilon, essential for leading-strand DNA replication and for the checkpoint.

82 n addition to proofreading and MMR influence leading-strand DNA replication fidelity.

83 us (AAV) replicates its DNA exclusively by a leading-strand DNA replication mechanism and requires co

84 that DNA polymerase epsilon participates in leading-strand DNA replication.

85 lagging-strand holoenzyme can occur without leading-strand DNA replication.

86 ese three altered helicases support rates of leading-strand DNA synthesis comparable to that observed

87 gene 5 DNA polymerase (gp5) are crucial for leading-strand DNA synthesis mediated by the replisome o

88 DNA faster, which allows it to keep up with leading-strand DNA synthesis overall.

89 t the interactions essential to initiate the leading-strand DNA synthesis remain unidentified.

90 -type fusions involving telomeres created by leading-strand DNA synthesis, reflective of a failure to

91 ease to process telomere ends synthesized by leading-strand DNA synthesis, thereby creating a termina

92 nthesis mediated by T7 DNA polymerase during leading-strand DNA synthesis.

93 specifically at those telomeres generated by leading-strand DNA synthesis.

94 G(2), specifically at telomeres generated by leading-strand DNA synthesis.

95 eration of a 3' overhang after completion of leading-strand DNA synthesis.

96 leading strand template, bypasses an intact leading strand DPC.

97 primary function is to synthesize DNA at the leading strand during replication.

98 oposed to induce resection that protects the leading-strand ends from NHEJ when TRF2 is absent.

99 s active despite its connection to a stalled leading strand enzyme.

100 ypothesis that DNA polymerase epsilon is the leading-strand enzyme, we observed no idling by this enz

101 l replication forks to synthesize continuous leading strands, even without ligase, supporting the sem

102 establishment of repressive chromatin on the leading strand following DNA synthesis may depend upon t

103 to guard against occasional slippage of the leading strand from the core channel.

104 mPol), plays a crucial role in the bypass of leading strand G4 structures.

105 ase, and 2) on the damaged template, nascent leading-strand gaps were generated by replisome lesion s

106 Conversely, ODNs that anneal to the leading strand generate fewer editing events although th

107 ments in the lagging strand or breaks in the leading strand generated by the mismatch-activated endon

108 efficient strand and (iv) the percentage of leading-strand genes in an bacterium can be accurately e

109 and proliferating cell nuclear antigen, long leading strands (>10 kb) are produced.

110 orescence microscopy, that the inhibition of leading-strand holoenzyme progression by gp59 is the res

111 n the leading strand as part of a 15-subunit leading-strand holoenzyme we refer to as CMGE.

112 ibosome have higher preferences to be on the leading strands; (ii) genes of some functional categorie

113 e mutations faster than those encoded on the leading strand in Bacillus subtilis.

114 ly proposed discontinuous replication of the leading strand in E. coli.

115 erases in replication of the lagging and the leading strands in human cells, respectively.

116 from the initial fork was elongated as a new leading-strand in the retrograde direction without laggi

117 We show that leading-strand initiation preferentially occurs within a

118 w that excision-proficient E. coli generates leading-strand intermediates >10-fold longer than laggin

119 Due to the anti-parallel nature of DNA, the leading strand is copied continuously, while the lagging

120 m the unhooked lesion ("insertion"), and the leading strand is extended beyond the lesion ("extension

121 polarity of duplex DNA necessitates that the leading strand is replicated continuously whereas the la

122 Although the leading strand is synthesized continuously, the lagging

123 bstacles in its path and may explain why the leading strand is synthesized discontinuously in vivo.

124 gression, even when the 3'-OH of the nascent leading strand is unavailable.

125 ting the lagging strand and G templating the leading strand; (iv) there is a strong bias for transiti

126 tion forks that collapse upon encountering a leading strand lesion are reactivated by a recombinative

127 ed for the DNA repair pathways described for leading strand lesion bypass and synthesis-dependent str

128 erase IV came at the expense of the inherent leading strand lesion skipping activity of the replisome

129 gment is synthesized beyond the point of the leading strand lesion.

130 daughter-strand gaps are generated opposite leading-strand lesions during the replication of ultravi

131 ic functions that Ctf18-RFC plays within the leading strand machinery via an interaction with the cat

132 9 cluster is required to facilitate telomere leading strand maturation and prevention of genomic inst

133 by producing 3 mature microRNAs: 1 from the leading strand (miR-146a), and 2 from the passenger stra

134 n fork structures, the presence of a nascent leading strand, modelling the effects of replication arr

135 Incisions are triggered when the nascent leading strand of a replication fork strikes the ICL Her

136 is skewed so that it is predominantly on the leading strand of chromosomal replication.

137 a strong bias for genes to be encoded on the leading strand of DNA, resulting in coorientation of rep

138 marily incorporated on the newly synthesized leading strand of nuclear DNA and were present upstream

139 In bacteria, most genes are on the leading strand of replication, a phenomenon attributed t

140 Most genes in bacteria are encoded on the leading strand of replication.

141 is defective, ribonucleotides in the nascent leading strand of the yeast genome are associated with r

142 e nascent single-stranded DNA (ssDNA) of the leading strand on active forks than on stalled forks.

143 wo lagging strands toward the center and two leading strands out the sides.

144 en suggested that the daughter strand of the leading strand partially dissociates from the parent str

145 tably as forks approach each other, and that leading strands pass each other unhindered before underg

146 proteins that catalyze DNA synthesis on the leading strand, plus the proteins required for lagging-s

147 t defective for mismatch repair (MMR) and/or leading strand (Polepsilon) or lagging strand (Poldelta)

148 rk is probably important for stabilizing the leading strand polymerase interactions with authentic re

149 e helicase and both DNA polymerases when the leading strand polymerase is blocked.

150 e polarity of DNA duplex, replication by the leading strand polymerase is continuous whereas that by

151 Furthermore, the blocked leading strand polymerase remains stably bound to the re

152 We reveal that, by being anchored to the leading strand polymerase, Ctf18-RFC can rapidly signal

153 ein-DNA complexes contain ssDNA ahead of the leading strand polymerase.

154 tly assigned polymerase (Pol) epsilon as the leading strand polymerase.

155 result of a complex formed between gp59 and leading-strand polymerase (gp43) on DNA that is instrume

156 The leading-strand polymerase advances in a continuous fashi

157 The helicase binds the leading-strand polymerase directly, but is connected to

158 nthesis, involves physical separation of the leading-strand polymerase from the replisome.

159 Instead, the leading-strand polymerase remains limited by the speed o

160 A beta hairpin from the leading-strand polymerase separates two parental DNA str

161 Leading-strand polymerase stalling at DNA damage impairs

162 ication likely results from a failure of the leading-strand polymerase still associated with the DNA

163 ntiparallel nature of duplex DNA permits the leading-strand polymerase to advance in a continuous fas

164 Thus, the cancer variant remains a dedicated leading-strand polymerase with markedly low accuracy.

165 s, the Cdc45-MCM-GINS (CMG) helicase and the leading-strand polymerase, Pol epsilon, form a stable as

166 he replisome because of its contact with the leading-strand polymerase.

167 ase so that it advances in parallel with the leading-strand polymerase.

168 ase so that it advances in parallel with the leading-strand polymerase.

169 eplisome-intrinsic responses is cessation of leading-strand polymerization, revealing this as a cruci

170 2 to 0.6 kb) were significantly shorter than leading strand products ( approximately 2 to 10 kb), and

171 plate, we obtained robust DNA synthesis with leading strand products of >20,000 nucleotides and laggi

172 itiated downstream of an unrepaired block to leading-strand progression, even when the 3'-OH of the n

173 dditional forks collide and displace nascent leading strands, providing yet more potential targets fo

174 tinue DNA synthesis without impediment, with leading strand re-priming by DnaG.

175 he conclusion that Polepsilon is the primary leading strand replicase and that Poldelta is restricted

176 ibutes to genomic stability via its roles in leading strand replication and the repair of damaged DNA

177 on protein, is required for normal, complete leading strand replication at telomeres.

178 he apparent lack of Poldelta contribution to leading strand replication is due to differential mismat

179 op, previously characterized in vitro at the leading strand replication origin (OH), is isolated as a

180 A polymerase epsilon, which is implicated in leading strand replication, incorporates one rNMP for ev

181 h recent evidence implicating Pol epsilon in leading strand replication, these data support a model o

182 ent formation of the imprint occur after the leading-strand replication complex has passed the site o

183 he identity of the major polymerase used for leading-strand replication is uncertain.

184 's mutational footprint suggests: (i) during leading-strand replication pol I is gradually replaced b

185 is enriched at lagging strands compared with leading-strand replication.

186 s information enabled an atomic model of the leading strand replisome.

187 The minimal reconstituted leading-strand replisome requires 24 proteins, forming t

188 rc1-Tof1-Csm3 (MTC) enhances the rate of the leading-strand replisome threefold.

189 d characterize their interaction with active leading-strand replisomes.

190 es further along the lagging strand than the leading strand, resulting in the exposure of long stretc

191 aucity of pol3-L612M-generated errors on the leading strand results from their more proficient remova

192 plication fork structures with and without a leading strand single-stranded DNA gap.

193 cleotide excision, further increased nascent leading-strand size to ~80 kb, while lagging-strand Okaz

194 This is the first direct proof of leading strand-specific replication by human POLE, which

195 ata reveal the first molecular mechanism for leading strand-specific telomere fragility and the first

196 These data suggest that FEN1 limits leading strand-specific telomere fragility by processing

197 y, but not DNA repair activities, results in leading strand-specific telomere fragility.

198 to facilitate RecA filament formation on the leading-strand ssDNA gaps generated by replisome lesion

199 The leading strand subsequently resumes synthesis, stalls ag

200 highly transcribed genes, are encoded on the leading strand such that transcription and replication a

201 obust on fork structures with no gaps in the leading strand, such as is found at the junction of a D

202 g strand synthesis decreases the rate of the leading strand, suggesting that lagging strand operation

203 the side channel, but in the open state, the leading strand surprisingly interacts with Cdc45.

204 delta universally participates in initiating leading strand synthesis and that nascent leading strand

205 -catalyzed DNA unwinding stimulate decoupled leading strand synthesis but not coordinated leading and

206 e results support the model of discontinuous leading strand synthesis in E. coli.

207 he protein-protein interface stabilizing the leading strand synthesis involves two distinct interacti

208 synthesis produce equal amounts of DNA, (ii) leading strand synthesis proceeds faster under condition

209 Leading strand synthesis requires PolC plus ten proteins

210 urrent but unsubstantiated model posits only leading strand synthesis starting at a nick near one cov

211 ng leading strand synthesis and that nascent leading strand synthesis switches from Pol epsilon to Po

212 However, 32 protein is not required for leading strand synthesis when helicase is loaded, less e

213 g strand synthesis proceeds much faster than leading strand synthesis, explaining why gaps between Ok

214 the lagging strand polymerase is faster than leading strand synthesis, indicating that replisome rate

215 he telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telom

216 rase epsilon (Polepsilon) is responsible for leading strand synthesis, whereas DNA polymerases alpha

217 apping functions of BLM and WRN helicase for leading strand synthesis.

218 r genomic replication and is responsible for leading strand synthesis.

219 tion of these replication complexes supports leading strand synthesis.

220 d, abortive DNA products are observed during leading strand synthesis.

221 ty of the polymerase-helicase complex during leading strand synthesis.

222 fusions involve only telomeres generated by leading strand synthesis.

223 ormed during copying of the G-rich strand by leading strand synthesis.

224 It supports both replisome assembly and leading strand synthesis; however, the underlying mechan

225 s the RNA transcript as a primer to continue leading-strand synthesis after the collision with RNA po

226 assay to provide real-time visualization of leading-strand synthesis by the S. cerevisiae replisome

227 , controlled by a molecular brake that halts leading-strand synthesis during primer synthesis.

228 and lagging-strand DNA synthesis by blocking leading-strand synthesis during the primosome assembly.

229 servation suggests a mechanism that prevents leading-strand synthesis from outpacing lagging-strand s

230 ork restart and the division of labor during leading-strand synthesis generally.

231 devoid of unwinding activity alone, supports leading-strand synthesis in the presence of T7 DNA polym

232 Leading-strand synthesis is then reinitiated downstream

233 e show that replication can be restarted and leading-strand synthesis re-initiated downstream of an u

234 is also crucial for efficient recoupling of leading-strand synthesis to CMG following lesion bypass.

235 occur when DNA polymerase epsilon catalyzes leading-strand synthesis together with its processivity

236 en these DNA polymerases also contributes to leading-strand synthesis under conditions of replicative

237 rprisingly also plays a role in establishing leading-strand synthesis, before DNA polymerase epsilon

238 DNA polymerase delta can support leading-strand synthesis, but at slower rates.

239 d and is proposed to recruit Pol epsilon for leading-strand synthesis, but to date a direct interacti

240 thesis proceeds downstream in the absence of leading-strand synthesis, involves physical separation o

241 ng coordination with the continuous and fast leading-strand synthesis.

242 hangs generated at the telomeres produced by leading-strand synthesis.

243 e transient pausing of the highly processive leading-strand synthesis.

244 enerated by lagging-strand synthesis than by leading-strand synthesis.

245 ision at ribonucleotides incorporated during leading-strand synthesis.

246 y monitoring the kinetics of loop growth and leading-strand synthesis.

247 y' during ongoing DNA synthesis and that the leading-strand T7 replisome does not pause during primer

248 Leading-strand telomere ends were not prone to fuse in t

249 MRE11 can also protect newly replicated leading strand telomeres from NHEJ by promoting 5' stran

250 ingle-stranded overhangs at newly replicated leading-strand telomeres to protect them from engaging t

251 its nuclease activity is required to protect leading-strand telomeres.

252 NM1B complex formation and the protection of leading-strand telomeres.

253 TRF1 binds BLM to facilitate lagging but not leading strand telomeric DNA synthesis.

254 d5 pathway when the lesion is located on the leading strand template and for the Rad52 pathway when t

255 A DPC on the leading strand template arrests the replisome by stallin

256 DNA endonuclease(s) unhooks an ICL from the leading strand template at a stalled replication fork si

257 ith the Escherichia coli replisome to bypass leading strand template damage, despite the fact that bo

258 ding of RecA on ssDNA regions exposed on the leading strand template of damaged forks, and do so by u

259 e effect of a noncoding DNA lesion in either leading strand template or lagging strand template on th

260 ssDNA must be exposed on the leading strand template to elicit this cooperativity, in

261 d when cloned in orientation II (CAGG on the leading strand template) rather than I and when cloned p

262 s observed where orientation II (CAGG on the leading strand template) was more prone to recombine.

263 of the G4 is dependent on it residing on the leading strand template, but is independent of its in vi

264 (CDC45, MCM2-7, GINS), which travels on the leading strand template, bypasses an intact leading stra

265 ical in targeting accessory helicases to the leading strand template, indicating an important role fo

266 eplisome encounters a blocking lesion in the leading strand template, the replication fork only trave

267 trand template much more readily than on the leading strand template.

268 s no evidence for a new priming event on the leading strand template.

269 Replication encounters with R-loops on the leading-strand template (co-directional) resulted in gap

270 e lagging-strand template (LGST) than in the leading-strand template (LDST).

271 Leading-strand template aberrations cause helicase-polym

272 e the replisome is stalled by collision with leading-strand template damage.

273 e the replisome is stalled by collision with leading-strand template damage.

274 in extensive degradation of the nascent and leading-strand template DNA and a loss of replication fo

275 se association with the helicase to copy the leading-strand template in a continuous manner while the

276 site-specific, cyclobutane pyrimidine dimer leading-strand template lesion provides only a transient

277 e of a collision between the replisome and a leading-strand template lesion remains poorly understood

278 erichia coli replisome transiently stalls at leading-strand template lesions and can either reinitiat

279 tions reveal that the replisome can tolerate leading-strand template lesions without dissociating by

280 ansiently when it encounters a lesion in the leading-strand template, skipping over the damage by rei

281 ing-strand template and at least once on the leading-strand template.

282 xposure of long stretches of single-stranded leading-strand template.

283 aB and Rep translocate along the lagging and leading strand templates, respectively, interact physica

284 ons, should be more strongly selected to the leading strand than singleton transcripts.

285 eplicative helicase enables synthesis of the leading strand to continue.

286 icase activation, the h2i clamps down on the leading strand to facilitate strand retention and regula

287 some prior to replication fork runoff on the leading strand to generate DSBs.

288 lesion bypass involves advance of a nascent leading strand to within one nucleotide of the ICL, foll

289 Eviction of the stalled helicase allows leading strands to be extended toward the ICL, followed

290 tial genes, which are strongly biased to the leading strand, to occur in operons.

291 ging-strand polymerase, Pol delta, binds the leading strand upon uncoupling and inhibits TLS.

292 rved in vitro but that, in vivo, the nascent leading strand was artifactually fragmented postsynthesi

293 ns-anti-benzo[a]pyrene-N(2)-dG lesion on the leading strand was efficiently and quickly recovered via

294 ting the lagging strand and T templating the leading strand, whereas G:C > A:T transitions preferenti

295 directional) resulted in gaps in the nascent leading strand, whereas lagging-strand template R-loops

296 old H3 is preferentially incorporated by the leading strand, whereas newly synthesized H3 is enriched

297 loads PCNA with a slight preference for the leading strand, which is dispensable for DNA replication

298 ier that Pol delta-PCNA is suppressed on the leading strand with CMG.

299 he lagging strand compared with those on the leading strand, with this difference being primarily in

300 his action results in a discontinuity in the leading strand, yet the replisome remains intact and bou