ライフサイエンスコーパス: lagging strand

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

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

3 synthesized DNA fragments into a contiguous lagging strand.

4 and positive regulation also operate on the lagging strand.

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

6 A polymerases alpha and delta synthesize the lagging strand.

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

8 result in repeat contractions in the nascent lagging strand.

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

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

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

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

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

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

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

16 driven by Okazaki fragment initiation on the lagging strand.

17 zaki-fragment synthesis on the discontinuous lagging strand.

18 reas newly synthesized H3 is enriched on the lagging strand.

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

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

21 red before undergoing ligation to downstream lagging strands.

22 ococcus replicating both the leading and the lagging strands.

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

24 een protein abundance on nascent leading and lagging strands.

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

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

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

28 hat simultaneously replicate the leading and lagging strands.

29 winding and annealing of nascent leading and lagging strands.

30 and synthesizes DNA at both the leading and lagging strands.

31 bited similar elongation between leading and lagging strands.

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

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

34 ging strand DNA replication templates, while lagging strand 3'-hydroxyl groups may prime endonuclease

35 nizes and enables tolerance of predominantly lagging strand abasic sites.

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

37 g cell nuclear antigen (PCNA) replicates the lagging strand and cooperates with flap endonuclease 1 (

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

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

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

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

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

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

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

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

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

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

48 s ~70x less frequently on the leading versus lagging strands, and that DNA replication in E. coli is

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

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

51 ication restart in bacteria by unwinding the lagging-strand arm of abandoned DNA replication forks an

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

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

54 1 is required to supplement FEN1 in maturing lagging strands at telomeres.

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

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

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

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

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

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

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

62 tly bound SSBs are removed from ssDNA by the lagging strand DNA polymerase without compromising the a

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

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

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

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

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

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

69 lease disproportionately cleaves predominant lagging strand DNA replication templates, while lagging

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

71 Lagging strand DNA synthesis by DNA polymerase requires

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

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

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

75 However, in the context of lagging strand DNA synthesis, the efficient disruption o

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

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

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

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

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

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

82 The lagging-strand DNA polymerase requires an oligoribonucle

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

84 ubunits, thereby challenging the notion that lagging-strand DNA polymerases frequently dissociate fro

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

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

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

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

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

90 nuclease-helicase implicated in DNA repair, lagging-strand DNA synthesis, and the recovery of stalle

91 ading strand, plus the proteins required for lagging-strand DNA synthesis, are essential for the reac

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

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

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

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

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

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

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

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

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

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

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

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

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

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 We find that Rad27 processes the majority of lagging-strand flaps, with a significant additional cont

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

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

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

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

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

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

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

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

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

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

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

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

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

122 ses alpha and delta for the synthesis of the lagging strand genome-wide, where it also shows a prefer

123 ransformed gene is encoded on the leading or lagging strand has limited influence on recombination ef

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

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

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

127 n PriA) near the ssDNA-dsDNA junction of the lagging strand in a PriA-DNA replication fork complex.

128 on, each Okazaki fragment synthesized on the lagging strand in eukaryotes must be nucleolytically pro

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

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

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

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

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

134 at the bottom of the ZF sub-ring, where the lagging strand is blocked and diverted sideways by OB ha

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

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

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

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

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

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

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

142 e asynchronous synthesis between leading and lagging strands leads to accumulation of single-stranded

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

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

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

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

147 By conditionally depleting lagging-strand nucleases and directly analyzing Okazaki

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

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

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

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

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

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

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

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

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

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

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

159 that after bypass CMGs encounter the nascent lagging strands of the converging fork and then transloc

160 nascent leading-strand size to ~80 kb, while lagging-strand Okazaki fragments remained unaffected.

161 ng-strand intermediates >10-fold longer than lagging-strand Okazaki fragments.

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

163 e show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis.

164 tion and show that Pol alpha-primase and the lagging-strand Pol delta can be re-used within the repli

165 (MMR) and/or leading strand (Polepsilon) or lagging strand (Poldelta) DNA polymerase proofreading.

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

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

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

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

170 ilitates the maximum replication rate of the lagging strand polymerase.

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

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

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

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

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

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

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

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

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

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

181 The lagging-strand polymerase sometimes recycles to begin th

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

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

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

185 Surprisingly, the main lagging-strand polymerase, Pol delta, binds the leading

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

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

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

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

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

191 Two lagging-strand polymerases are attached to the primase,

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

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

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

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

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

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

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

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

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

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

202 espectively, perform the bulk of leading and lagging strand replication of the eukaryotic nuclear gen

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

204 the major driver of nick translation during lagging strand replication, Pif1-dependent stimulation o

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

206 on, which together result in the complicated lagging strand replication.

207 used by unwarranted Pif1 interference during lagging strand replication.

208 recipient, early in conjugal transfer, until lagging-strand replication creates the double-stranded f

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

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

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

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

215 delta (Poldelta) synthesize the leading and lagging strands, respectively.

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

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

218 2, 5'-flaps are thought to accumulate on the lagging strand, resulting in DNA damage-checkpoint arres

219 eta dependent signature is also found to be lagging strand specific in patients with skin cancer.

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

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

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

223 incorporated nucleotides during leading and lagging strand syntheses.

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

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

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

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

228 Lagging strand synthesis proceeds much faster than leadi

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

230 ropose underlies polymerase recycling during lagging strand synthesis, in analogy to Escherichia coli

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

232 bonucleotides for DNA polymerase to initiate lagging strand synthesis.

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

234 motif is required for pol eta to function in lagging strand synthesis.

235 lalpha might install the mat1 imprint during lagging strand synthesis.

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

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

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

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

240 nings, we identified five core components of lagging-strand synthesis as essential for cccDNA formati

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

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

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

244 Lagging-strand synthesis is a complex event requiring re

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

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

247 the contributions of individual nucleases to lagging-strand synthesis nor the structure of the DNA in

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

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

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

251 esions, are always associated with continued lagging-strand synthesis, are observed when either Pol e

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

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

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

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

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

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

258 ion of the impact of Rad27, Dna2 and Exo1 on lagging-strand synthesis.

259 Repeats contract in the course of lagging-strand synthesis: The processivity subunit of DN

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

261 e analysis of BrdU uptake during leading and lagging-strand telomere replication shows preferential u

262 Lagging-strand telomeres lacking TRF1 or BLM form fragil

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

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

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

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

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

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

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

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

271 oth ahead of the replication fork and on the lagging strand template.

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

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

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

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

276 rmed that APOBEC3A modifies cytosines in the lagging-strand template during replication and in short

277 3A) and APOBEC3B, deaminate cytosines in the lagging-strand template during replication.

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

279 We propose that accumulation of ssDNA in the lagging-strand template fosters the formation of a tripl

280 lation of single-stranded DNA (ssDNA) in the lagging-strand template greatly increases the probabilit

281 gaps in the nascent leading strand, whereas lagging-strand template R-loops (head-on) had little imp

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

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

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

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

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

287 ase, which can resolve G-quadruplexes on the lagging-strand template.

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

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

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

291 the DPC activates SPRTN on both leading and lagging strand templates.

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

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

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

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

296 CMGs nearly face each other, placing the two lagging strands toward the center and two leading strand

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

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

299 C complex preferentially loads PCNA onto the lagging strand, which is crucial for DNA replication but

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