ライフサイエンスコーパス: lagging strand

1 n the leading strand and by Pol delta on the lagging strand.

2 tightly to Pol delta and recruits it to the lagging strand.

3 is and determine that 17% of them are on the lagging strand.

4 s RNA primers before hand-off to PolC at the lagging strand.

5 on machineries when genes are encoded on the lagging strand.

6 not even consider the ones biased toward the lagging strand.

7 g strand and of each Okazaki fragment on the lagging strand.

8 switching by 3' exonucleases targeted to the lagging strand.

9 ion of the ODN during replication within the lagging strand.

10 driven by Okazaki fragment initiation on the lagging strand.

11 ment could be removed before ligation to the lagging strand.

12 ter Pol delta activity or position it on the lagging strand.

13 ve exchange of polymerases during TLS on the lagging strand.

14 synthesized DNA fragments into a contiguous lagging strand.

15 k was ligated by DNA ligase to form a mature lagging strand.

16 ion processes that occur for the leading and lagging strands.

17 een protein abundance on nascent leading and lagging strands.

18 dicated to bulk synthesis of the leading and lagging strands.

19 bited similar elongation between leading and lagging strands.

20 ed forks, PCNA is unloaded specifically from lagging strands.

21 two-nuclease pathway of primer processing on lagging strands.

22 of the mutations between the leading and the lagging strands.

23 hat simultaneously replicate the leading and lagging strands.

24 winding and annealing of nascent leading and lagging strands.

25 ed to sliding clamps on both the leading and lagging strands.

26 ects the core polymerases on the leading and lagging strands.

27 ions whereas other sites bind the leading or lagging strands.

28 red before undergoing ligation to downstream lagging strands.

29 ococcus replicating both the leading and the lagging strands.

30 d is stopped by a block on the non-tracking (lagging) strand.

31 amp machinery directs quality control on the lagging strand and CMG enforces quality control on the l

32 s preferentially occur with C templating the lagging strand and G templating the leading strand; (iv)

33 ion fork, synthesis of RNA primers along the lagging strand and hand-off to DnaEBs.

34 s preferentially occur with A templating the lagging strand and T templating the leading strand, wher

35 primer terminus, single-stranded leading and lagging strands and duplex in immediate proximity of the

36 equired for polymerase stalling on telomeric lagging strands and suggest that an alternative mechanis

37 sequence composition between the leading and lagging strands and the error bias for DNA polymerase in

38 ts within the duplex region on the tracking (lagging) strand and strong contacts with the displaced l

39 ditions that disable primer synthesis on the lagging strand, and (iii) conditions that accelerate hel

40 ng protein (SSB) to bind to the ssDNA on the lagging strand, and a helicase loader that associates wi

41 der specifically inhibits Pol epsilon on the lagging strand, and CMG protects Pol epsilon against RFC

42 structure that models a fork with a nascent lagging strand, and the unwinding action of HEL308 is sp

43 Genes encoded in the lagging strand are transcribed such that RNA polymerase

44 verage rates of DNA synthesis on leading and lagging strands are similar, individual trajectories of

45 genome is discontinuously replicated on the lagging strand as Okazaki fragments.

46 tion fork structures containing a gap in the lagging strand as short as 15 nucleotides, suggesting th

47 1 is required to supplement FEN1 in maturing lagging strands at telomeres.

48 nstitute replication of both the leading and lagging strands at the physiological rate.

49 g reveals polymerases remaining bound to the lagging strand behind the replication fork, consistent w

50 origin activation; synthesis of leading and lagging strands by the three replicative DNA polymerases

51 These lagging-strand clamps are thought to be bound by the rep

52 of point mutations in the core genes on the lagging strand compared with those on the leading strand

53 and show that the PCNA clamp is enriched at lagging strands compared with leading-strand replication

54 ired for Exo1 5'-exonuclease activity on the lagging strand daughter DNA, but its DNA binding activit

55 es Exo1-mediated exonuclease activity on the lagging strand DNA by facilitating Exo1 loading onto a s

56 myces cerevisiae polymerase (Pol) delta, the lagging strand DNA polymerase.

57 ng the main leading strand and Pol delta the lagging strand DNA polymerase.

58 silon) arrived at telomeres earlier than the lagging strand DNA polymerases alpha (Polalpha) and delt

59 led SSB shows defects in coupled leading and lagging strand DNA replication and does not support repl

60 9), accumulate low molecular weight, nascent lagging strand DNA replication intermediates at telomere

61 ctions in providing inherent flexibility for lagging strand DNA replication or inherent stability for

62 that flap endonuclease 1 (FEN1), a canonical lagging strand DNA replication protein, is required for

63 conversion to abasic sites ahead of nascent lagging strand DNA synthesis and subsequent bypass by er

64 Lagging strand DNA synthesis by DNA polymerase requires

65 idate for serving as the primase to initiate lagging strand DNA synthesis during normal replication a

66 rt oligoribonucleotide primers that initiate lagging strand DNA synthesis or reprime DNA synthesis af

67 that are aimed at reconstituting leading and lagging strand DNA synthesis separately and as an integr

68 ular DNA templates and monitored leading and lagging strand DNA synthesis using the strand-specific i

69 bonucleotides required for the initiation of lagging strand DNA synthesis.

70 ase activity, and to function in leading and lagging strand DNA synthesis.

71 bonucleotides required for the initiation of lagging strand DNA synthesis.

72 o a replisome capable of coordinated leading/lagging strand DNA synthesis.

73 t synthesis, with important implications for lagging strand DNA synthesis.

74 s-syn TT dimer carried on the leading or the lagging strand DNA template in a plasmid system we have

75 strand DNA polymerase epsilon as compared to lagging-strand DNA polymerase delta.

76 larly damaging for cells with defects in the lagging-strand DNA polymerase delta.

77 The lagging-strand DNA polymerase requires an oligoribonucle

78 rand of the replication fork to reorient the lagging-strand DNA polymerase so that it advances in par

79 lisome and to aid delivery of primers to the lagging-strand DNA polymerase.

80 In yeast, replicative leading- and lagging-strand DNA polymerases (Pols epsilon and delta,

81 ule analysis, we establish that leading- and lagging-strand DNA polymerases function independently wi

82 highly dynamic picture of the replisome with lagging-strand DNA polymerases residing at the fork for

83 During lagging-strand DNA replication in eukaryotic cells prime

84 to salt-dependent uncoupling of leading- and lagging-strand DNA synthesis and to a surprising obstruc

85 Chromatin promotes the regular priming of lagging-strand DNA synthesis by facilitating DNA polymer

86 unit is encoded by POLD1, is responsible for lagging-strand DNA synthesis during DNA replication.

87 delta perform the bulk of yeast leading- and lagging-strand DNA synthesis.

88 ir implications for coordinated leading- and lagging-strand DNA synthesis.

89 ng-strand DNA and discontinuous synthesis of lagging-strand DNA.

90 In the closed state, the lagging strand does not pass through the side channel, b

91 osome complexes to initiate synthesis on the lagging strand during DNA replication.

92 y of polymerases and synthesizes most of the lagging strand during DNA replication.

93 at these cassettes preferentially target the lagging strand during DNA replication.

94 ocessed RNA is incorporated as a provisional lagging strand during mtDNA replication.

95 Pol delta synthesizes the lagging strand during replication of genomic DNA and als

96 e as cruciforms or fold into hairpins on the lagging strand during replication.

97 stand of the viral genome, which is also the lagging strand during viral DNA replication.

98 DNA priming role may be shared on leading or lagging strands during DNA replication.

99 Specific perturbation of lagging strand elongation on minicircles with a highly a

100 strand, but it is unable to function on the lagging strand, even when Pol delta is not present.

101 niques are combined to examine the effect of lagging strand events on the Escherichia coli replisome

102 Overall, lagging strand events that impart negative effects on th

103 lowers replisome processivity but only when lagging strand extension is inoperative.

104 plex using the 2B subdomain and reels in the lagging strand, extruding a single-stranded loop.

105 The architecture suggests that lagging-strand extrusion initiates in the middle of the

106 ovements cause the DNA strand separation and lagging-strand extrusion.

107 action requires the 9-1-1 clamp and the Dna2 lagging-strand factor and is distinguishable from Mec1's

108 tions with the DNA primase complex supported lagging strand formation as well.

109 g strand products of >20,000 nucleotides and lagging strand fragments from 600 to 9,000 nucleotides a

110 d fork reversal with substrates that contain lagging strand gap.

111 compatible with their role in the repair of lagging strand gaps at stalled replication forks.

112 nucleotides (ODNs) designed to anneal to the lagging strand generate 100-fold greater 'editing' effic

113 We previously reported that lagging-strand genes accumulate mutations faster than th

114 C, and the recombination protein, RecA, with lagging-strand genes increases in a transcription-depend

115 nism leading to the increased mutagenesis of lagging-strand genes remained unknown.

116 ases lesion susceptibility of, specifically, lagging-strand genes, activating an Mfd-dependent error-

117 otes efficient replisome progression through lagging-strand genes, thereby reducing potentially detri

118 These encounters increase mutagenesis in lagging-strand genes, where replication-transcription co

119 s also required for increased mutagenesis of lagging-strand genes.

120 ally, underlies the accelerated evolution of lagging-strand genes.

121 In this study, the human lagging strand holoenzyme was reconstituted in vitro.

122 iption factor have higher preferences on the lagging strands; (iii) there is a balancing force that t

123 he percentage of genes on the leading versus lagging strand in a genome.

124 uctures on the templates of the leading- and lagging-strands in a replication-dependent reaction.

125 ing mutations are more commonly found on the lagging strand, indicating faster adaptive evolution in

126 coding region (NCR) and one at the prominent lagging-strand initiation site termed Ori-L.

127 PcrA preferentially translocates on the DNA lagging strand instead of unwinding the template duplex.

128 The processing of lagging-strand intermediates has not been demonstrated i

129 ity to produce ligatable products with model lagging-strand intermediates in the presence of the wild

130 e and DNA helicase, whereas synthesis of the lagging strand involves interactions of these proteins w

131 ing strand is copied continuously, while the lagging strand is produced by repeated cycles of priming

132 trand is replicated continuously whereas the lagging strand is replicated in discrete segments known

133 of DNA replication, primase activity on the lagging strand is required throughout the replication pr

134 ding strand is synthesized continuously, the lagging strand is synthesized in small segments designat

135 anism in which synthesis of both leading and lagging strands is frequently interrupted.

136 consisting of the paired nascent leading and lagging strands is produced, is observed under condition

137 T pathway preferentially occurs at telomeric lagging strands leading to heterogeneous telomere length

138 d CTG repeat deletion exclusively during DNA lagging strand maturation and base excision repair.

139 te S phase, either by physical uncoupling of lagging strand maturation from the fork progression, or

140 that fork movement is not tightly coupled to lagging strand maturation.

141 Leading and lagging strand minicircle progeny similarly declined dur

142 We find that repair of genomic lagging strand mismatches occurs bi-directionally in E.

143 nt to a sliding clamp, the polymerase on the lagging strand must cycle on and off DNA for each Okazak

144 s the primase-helicase and RNA primer on the lagging strand of a model replication fork, the second p

145 t interacts with DNA polymerase alpha in the lagging strand of DNA during replication.

146 whether the oligo anneals to the leading or lagging strand of DNA replication, or whether phosphorot

147 annealing synthetic oligonucleotides at the lagging strand of DNA replication.

148 ypass of GO lesions is more efficient on the lagging strand of replication and requires an interactio

149 was part of the newly synthesized leading or lagging strand of replication.

150 leotides and accessible ssDNA targets on the lagging strand of the replication fork are limiting fact

151 ature to increase the amount of ssDNA at the lagging strand of the replication fork that is available

152 is solved by the formation of a loop in the lagging strand of the replication fork to reorient the l

153 hesize DNA and repair discontinuities on the lagging strand of the replication fork.

154 licates and matures Okazaki fragments on the lagging strand of the replication fork.

155 ast, although Pol delta contacts the nascent lagging strands of active and stalled forks, it binds to

156 ide association of proteins with leading and lagging strands of DNA replication forks.

157 rate of the leading strand, suggesting that lagging strand operations exert a drag on replication fo

158 uch as gaps between Okazaki fragments in the lagging strand or breaks in the leading strand generated

159 been proposed for triggering release of the lagging strand polymerase at the replication fork, enabl

160 ports the idea that Pol delta is primarily a lagging strand polymerase during replication across the

161 Further, the lagging strand polymerase is faster than leading strand

162 Instead, the stalled lagging strand polymerase recycles from the lesion and i

163 The primosome and the lagging strand polymerase remain active during this peri

164 f DNA polymerases; defects in DNA pol delta (lagging strand polymerase) and Mgs1 (a pol delta interac

165 interacts with the Mcm2-7 core helicase, the lagging strand polymerase, DNA polymerase-alpha and the

166 helicase, primase, leading polymerase and a lagging strand polymerase.

167 directly, but is connected to the Pol alpha lagging-strand polymerase by the trimeric adaptor Ctf4.

168 d hand-off to the polymerase; and third, the lagging-strand polymerase copies DNA faster, which allow

169 that cause lower processivity and transient lagging-strand polymerase dissociation from DNA.

170 r data indicate that unrepaired leading- and lagging-strand polymerase errors drive extinction within

171 We find that the lagging-strand polymerase frequently releases from an Ok

172 his process proceeds through transfer of the lagging-strand polymerase from the beta sliding clamp le

173 Considering that the lagging-strand polymerase has to recycle after the compl

174 se advances in a continuous fashion, but the lagging-strand polymerase is forced to restart at short

175 Instead, the lagging-strand polymerase is simply less processive in t

176 Interestingly, when the lagging-strand polymerase is supplied with primed DNA in

177 vity of Pol epsilon is compromised more than lagging-strand polymerase Pol delta at low dNTP concentr

178 Disrupting chromatin assembly or lagging-strand polymerase processivity affects both the

179 NA from primer synthesis in initiating early lagging-strand polymerase recycling.

180 The lagging-strand polymerase sometimes recycles to begin th

181 ill associated with the DNA helicase and the lagging-strand polymerase that are proceeding downstream

182 this signal requires no transmission to the lagging-strand polymerase through protein or DNA interac

183 les of RNA primer synthesis, transfer to the lagging-strand polymerase, and extension effected by coo

184 tion, as expected for a processive, recycled lagging-strand polymerase.

185 d by cooperation between DNA primase and the lagging-strand polymerase.

186 stalled replication forks by the leading and lagging strand polymerases and that accumulation of thes

187 plex were required to couple the leading and lagging strand polymerases at the replication fork.

188 ome by the extra grip on DNA provided by the lagging strand polymerases.

189 nt models of primer transfer to leading- and lagging strand polymerases.

190 Our data suggest that lagging-strand polymerases are exchanged at a frequency

191 Further, new lagging-strand polymerases are readily recruited from a

192 the physical connection between leading- and lagging-strand polymerases causes the daughter strands t

193 sumed that DNA synthesis by the leading- and lagging-strand polymerases in the replisome must be coor

194 We show that loops in the lagging strand predominantly occur during priming and on

195 synthesis, respectively, on the leading and lagging strands, preformed processed RNA is incorporated

196 ssential role for the chi/SSB interaction in lagging-strand primer utilization is not supported.

197 Lagging strand products ( approximately 0.2 to 0.6 kb) w

198 replication complex synthesized leading and lagging strand products at molar ratios varying between

199 t stimulated primer synthesis led to shorter lagging strand products.

200 and increased the length of both leading and lagging strand products.

201 ion of synthesis of an Okazaki fragment, the lagging strand replicase must recycle to the next primer

202 DnaE does not serve as the lagging strand replicase, like DNA polymerase delta in e

203 onuclease 1 and replication protein A in DNA lagging strand replication and with BLM/Sgs1 and MRN/X i

204 mes more mismatches produced in cells during lagging strand replication compared with the leading str

205 bstitution rates are similar for leading and lagging strand replication, but are higher in regions re

206 e show that, consistent with its function in lagging strand replication, human (h) FEN1 could cleave

207 Pol delta and Pol alpha, which conduct lagging strand replication, incorporate one rNMP for eve

208 this complex is integral to every aspect of lagging strand replication.

209 heterogeneity and variations in leading- and lagging-strand replication fidelity and mismatch repair,

210 vy-strand DNA sequences, implicating them as lagging-strand replication intermediates.

211 a), which initiates Okazaki fragments during lagging-strand replication, will always be closer to a 5

212 o explain some controversial features of the lagging-strand replication.

213 , which takes over for Pol alpha to complete lagging-strand replication.

214 mismatches are generated during leading- and lagging-strand replication.

215 Polymerase delta is widely accepted as the lagging strand replicative DNA polymerase in eukaryotic

216 We have reconstituted a eukaryotic leading/lagging strand replisome comprising 31 distinct polypept

217 Pol delta, that function on the leading and lagging strands, respectively.

218 hPol delta in the replication of leading and lagging strands, respectively.

219 The lagging strand significantly increases the processivity

220 es, initiating synthesis on both leading and lagging strand single-stranded DNA templates.

221 mer extension by DnaEBs are carried out by a lagging strand-specific subcomplex comprising DnaG, DnaE

222 Other results indicate that Gp32 binding to lagging strand ssDNA relieves the blockage of Gp43 polym

223 imposes unique events that occur only on the lagging strand, such as primase binding to DnaB helicase

224 d synthesis requires PolC plus ten proteins; lagging strand synthesis additionally requires primase a

225 genome replication that involves leading and lagging strand synthesis and is consistent with the requ

226 polymerases in eukaryotic cells, catalyzing lagging strand synthesis as well as playing a role in ma

227 would allow the coordination of leading and lagging strand synthesis at a replication fork.

228 Interestingly, lagging strand synthesis decreases the rate of the leadi

229 ves an unanticipated intermediate step where lagging strand synthesis is delayed until telomerase is

230 bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long s

231 Lagging strand synthesis proceeds much faster than leadi

232 ded by our observations that (i) leading and lagging strand synthesis produce equal amounts of DNA, (

233 The antiparallel structure of DNA requires lagging strand synthesis to proceed in the opposite dire

234 bonucleotides for DNA polymerase to initiate lagging strand synthesis.

235 because of its collision-and-release role in lagging strand synthesis.

236 mers and may functionally couple leading and lagging strand synthesis.

237 nd synthesis but not coordinated leading and lagging strand synthesis.

238 f oligoribonucleotides for the initiation of lagging strand synthesis.

239 pha that primes each Okazaki fragment during lagging strand synthesis.

240 fy the exchange dynamics for PolC engaged in lagging strand synthesis.

241 vivo, and reveal the interconnection between lagging-strand synthesis and chromatin assembly.

242 These results broaden our understanding of lagging-strand synthesis and emphasize the stability of

243 erase I (pol I) processes RNA primers during lagging-strand synthesis and fills small gaps during DNA

244 ricts fork movements, uncouples leading- and lagging-strand synthesis and generates small single-stra

245 ppresses the loss of telomeres replicated by lagging-strand synthesis by a yet to be defined mechanis

246 We report here that template unwinding and lagging-strand synthesis continue downstream of the lesi

247 hin the replisome, providing a new model for lagging-strand synthesis in eukaryotes that resembles th

248 Lagging-strand synthesis is a complex event requiring re

249 Lagging-strand synthesis is mediated via a replication l

250 and cooperative interaction with FEN1 during lagging-strand synthesis may serve to regulate sequentia

251 Here, we discuss a surprising, alternative lagging-strand synthesis mechanism: efficient replicatio

252 that polymerase uncoupling, where extensive lagging-strand synthesis proceeds downstream in the abse

253 Here we show that Rad53 couples leading- and lagging-strand synthesis under replication stress.

254 thesis across hard-to-replicate sites and in lagging-strand synthesis with polymerase delta (Poldelta

255 ty function (i) applies to both leading- and lagging-strand synthesis, (ii) is independent of Pol IV,

256 DNA polymerase delta is required for lagging-strand synthesis, but surprisingly also plays a

257 rolonged cell culture, emetine inhibition of lagging-strand synthesis, or slowing of DNA synthesis by

258 polymerases during coordinated leading- and lagging-strand synthesis.

259 mechanisms for coordination of leading- and lagging-strand synthesis.

260 fork, reflecting their roles in leading- and lagging-strand synthesis.

261 thout requiring coordination of leading- and lagging-strand synthesis.

262 facilitating replication through the G-rich lagging strand telomere, thereby ensuring high fidelity

263 Here, we show that this mutation impairs lagging-strand telomere replication and leads to the acc

264 ease 1 (FEN1) is required for replication of lagging strand telomeres.

265 ecruitment of telomerase to leading- but not lagging-strand telomeres of budding yeast.

266 the formation of G-quadruplex structures at lagging-strand telomeres to promote shelterin associatio

267 As the template for lagging strand telomeric DNA synthesis is the TTAGGG rep

268 ol delta) is responsible for replicating the lagging strand template and anchors to the proliferating

269 ract with ssDNA on either the leading or the lagging strand template at forks.

270 Inhibition of Rep binding to the lagging strand template by competition with SSB might th

271 A damaged base in the lagging strand template does not affect the progression

272 s to specific G-rich/G4 motif located on the lagging strand template for DNA replication and supports

273 at replisomes bypass large roadblocks on the lagging strand template much more readily than on the le

274 lesion in either leading strand template or lagging strand template on the bacteriophage T4 replisom

275 A DPC on the lagging strand template only transiently stalls the repl

276 d high helicase-primase concentrations and a lagging strand template whose sequence resembled that of

277 f UL5 and UL52 in opposite directions on the lagging strand template, and they identify molecular com

278 at Poldelta is restricted to replicating the lagging strand template.

279 iral origin and each Okazaki fragment on the lagging strand template.

280 tly more cytosines mutated to thymine in the lagging-strand template (LGST) than in the leading-stran

281 In all of these examples, the lagging-strand template appears to be targeted using a v

282 ODNs targeting the lagging-strand template blocked the time-dependent or em

283 idence that APOBEC mutagenesis occurs on the lagging-strand template during DNA replication.

284 ) complementary to the (CTG)(45) . (CAG)(45) lagging-strand template eliminated DNA hairpin formation

285 dress the idea that features specific to the lagging-strand template represent vulnerabilities that a

286 ted palindrome, which forms a hairpin on the lagging-strand template that is processed to form breaks

287 ce during ongoing DNA synthesis; the nascent lagging-strand template therefore organizes into a primi

288 anscripts are successively hybridized to the lagging-strand template, as the replication fork advance

289 phosphate-steering promotes an unanticipated lagging-strand template-switch mechanism during replicat

290 t predominantly the CCG strand serves as the lagging-strand template.

291 hich polymerases are copying the leading and lagging strand templates (Johnson et al, 2015).

292 on, it is likely that TLS on the leading and lagging strand templates is unique for each strand.

293 current understanding of TLS on leading and lagging strand templates, and propose testable hypothese

294 inated DNA hairpin formation on leading- and lagging-strand templates and relieved fork stalling.

295 and other proteins to copy the leading- and lagging-strand templates at rates between 1 and 2 kb min

296 , DNA synthesis progresses further along the lagging strand than the leading strand, resulting in the

297 replication requires one daughter strand-the lagging strand-to be synthesised as a series of disconti

298 consisting of the paired nascent leading and lagging strands, whereas RuvC cleaves the Holliday junct

299 ted preferential elongation of the telomeric lagging strands, whereas telomerase positive cells exhib

300 3, 4, 6, and 7, but not 2 and 5, engage the lagging strand with an approximate step size of one base