ライフサイエンスコーパス: fork

1 control helicase-polymerase coupling at the fork.

2 ror-prone DNA polymerases to the replication fork.

3 the nuclease domain to incise one arm of the fork.

4 s recruitment of multiple holoenzymes at the fork.

5 the fork protection complex at a replication fork.

6 es are disrupted in front of the replication fork.

7 stabilizers that travel with the replication fork.

8 ution of DNA topological stress ahead of the fork.

9 sive MRE11-dependent degradation of reversed forks.

10 nd both NER bubble junctions and replication forks.

11 ain genomic integrity by stabilizing stalled forks.

12 caused by unrepaired DNA gaps at replication forks.

13 by the Y-shaped DNA structure of replication forks.

14 vated by R loop-induced reversed replication forks.

15 mediated homologous recombination at stalled forks.

16 tivate HR at stalled forks or behind ongoing forks.

17 ates the enzymatic activities at replication forks.

18 1 nucleofilaments at damaged DNA replication forks.

19 e effect of protein obstacles on replication forks.

20 cleoprotein complexes, can block replication forks.

21 g MRE11-dependent degradation of replication forks.

22 rs CMG ubiquitylation at stalled replication forks.

23 s that hinder the progression of replication forks.

24 imit its association and activity at stalled forks.

25 otherapeutics causes reversal of replication forks.

26 is required for their recruitment to stalled forks.

27 unctional maintenance of stalled replication forks.

28 le for TIM in protecting stalled replication forks.

29 y leading to the collapse of DNA replication forks.

30 e-strand (ss) DNA and initiate bidirectional forks.

31 tivity and symmetric movement of replication forks.

32 ell cycle and is associated with replication forks.

33 stabilizes telomeres and stalled replication forks.

34 al replication rates and stabilizing stalled forks.

35 hat fine-tunes MUS81 activity at replication forks.

36 speed without affecting the number of active forks.

37 hich promotes restart of stalled replication forks.

38 and restart of stalled telomere replication forks.

39 dation of nascent DNA at stalled replication forks.

40 ter DNA lesions, which can stall replication forks.

41 oss of cohesion, possibly at DNA replication forks.

42 resection of HU-induced stalled replication forks.

43 rating topological stress and conflicts with forks(1,2).

44 ed de novo onto nascent DNAs associated with forks, a process that would be dependent on cohesin's Sc

45 king out the forked gene in the mosquito (Ae-Forked; a known actin-bundling protein) by CRISPR-Cas9 g

46 In the absence of EXO1, forks accumulate at stabilized G-quadruplexes and ultima

47 secondary structures that stall replication forks, activate the ATR checkpoint kinase, and require u

48 and also to protect stressed DNA replication forks against spurious nucleolytic attrition.

49 is a protein complex on the DNA replication fork and functions in a dynamic environment at the inter

50 e gap-filling in the wake of the replication fork and incomplete Okazaki fragment maturation, which i

51 9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to trans

52 he nascent lagging strands of the converging fork and then translocate along double-stranded DNA (dsD

53 istinct from mechanisms engaged at collapsed-forks and breaks within repeated sequences.

54 llel to Chl1 and Mrc1 to protect replication forks and cell viability.

55 ant 273H and PARP1 interact with replication forks and could serve as potential biomarkers for breast

56 gh these versatile activities at replication forks and DNA damage sites, DNA2 functions as both a tum

57 s needed to restart DNA synthesis at stalled forks and promote survival following replication stress,

58 ded DNA-binding complex, localize at stalled forks and protect stalled forks from degradation by the

59 tein, FANCD2, locates to stalled replication forks and recruits homologous recombination (HR) factors

60 that LSD1 associates with HSV-1 replication forks and replicating viral DNA, suggesting that it may

61 ng to nascent-strand degradation at reversed forks and ssDNA accumulation.

62 CA2 DNA repair associated (BRCA2) to stalled forks and that in their absence, nascent DNA strands at

63 ereby aiding TIM localization to replication forks and the coordination of replisome progression.

64 HAT) that regulates the stability of stalled forks and the response to PARP inhibition in BRCA1/2-def

65 depends on the number of active replication forks and their velocity.

66 r periphery, associates with DNA replication forks, and counteracts TOP1ccs during DNA replication.

67 obstacles to the replisome, deal with broken forks, and impact human health and disease.

68 n firing, of the architecture of replication forks, and of the functional organization of the replica

69 poisomerase reactions, collapsed replication forks, and other stressors.

70 vAB-dependent reestablishment of replication fork; and efficiencies of degradosome machinery and RNA

71 We demonstrated that actin bundles and Ae-Forked are required for bristle elongation, but not for

72 In this Review, we discuss how replication forks are actively stalled, remodelled, processed, prote

73 absence, nascent DNA strands at unprotected forks are degraded by MRE11 homolog double-strand break

74 radation and collapse of stalled replication forks are main sources of genomic instability, yet the m

75 Without this response, stalled replication forks are not stabilized, and new origin firing cannot b

76 These collapsed forks are preferentially repaired via error-prone end jo

77 out the cell cycle and regardless of whether forks are replicating or stalled.

78 rogression, but the details of how uncoupled forks are restarted remain uncertain.

79 nd the protection of stalled DNA replication forks are thought to underlie the chemosensitivity of tu

80 Upon replication fork arrest, the replication checkpoint kinase Cds1 is s

81 Several replication-fork-associated "cohesion establishment factors," includ

82 Cell, Kim et al., 2020 report that PCAF is a fork-associated histone acetyltransferase (HAT) that reg

83 ltransferase PCAF (p300/CBP-associated) as a fork-associated protein that promotes fork degradation i

84 in patient cells, accompanied by replication fork asymmetry, increased interorigin distances, replica

85 d for replicative helicases at a replication fork at atomic resolution, a prerequisite to understandi

86 tion checkpoint (DRC), the stable pausing of forks at protein fork blocks, the coupling of DNA helica

87 s of challenged and unchallenged replication forks, averaged across S phase, and model a single speci

88 Using replication fork barriers in fission yeast, we report that relocatio

89 e: cooperative origin firing and replication fork barriers.

90 e of a 'battleground' at the DNA replication fork between homologous recombination (HR) factors and L

91 and balances PCNA levels at the replication fork, beyond the needs of DNA replication, to promote es

92 Instead of utilizing a canonical replication fork, BIR is driven by a migrating D-loop and is associa

93 ully replicate DNA and cope with replication fork blocks and stalling, while simultaneously promoting

94 DRC), the stable pausing of forks at protein fork blocks, the coupling of DNA helicase and polymerase

95 In contrast, fork-bound SSB loads PriA onto the duplex DNA arms of fo

96 (SSB) is typically present at the abandoned forks, but it is unclear how SSB and PriA interact, alth

97 ricts excessive DNA unwinding at replication forks by limiting CMG helicase activity, suggesting a me

98 ATR prevents excessive cleavage of reversed forks by MUS81, revealing a MUS81-triggered and ATR-medi

99 Stalled replication forks can be restarted and repaired by RAD51-mediated ho

100 d cell cluster that contained VENs, but also fork cells and a subset of pyramidal neurons.

101 When arginine fork chemical recognition principles were applied to exi

102 experimental data, suggesting the utility of fork classifications to improve structural models.

103 ck fork degradation, but it does not prevent fork collapse and cell sensitivity in the presence of re

104 zation of DNA or RNA, leading to replication fork collapse or transcription arrest, or can serve as m

105 impede DNA replication and cause replication fork collapse.

106 ecBCD complex bound to several different DNA forks containing a Chi sequence, including one in which

107 ZF motifs helps recruit NEIL3 to replication forks converged at an ICL, but the nature of DNA binding

108 second repair mechanism requires replication fork convergence, but does not involve DNA incisions-ins

109 A fiber analyses reveal that PRIMPOL rescues fork degradation by reinitiating DNA synthesis past DNA

110 ) as a fork-associated protein that promotes fork degradation in BRCA-deficient cells by acetylating

111 Here, we show that fork degradation is no longer detectable in BRCA1-defici

112 show that in BRCA2-deficient cells, rescuing fork degradation might not be sufficient to ensure fork

113 ng MRE11 in BRCA2-deficient cells does block fork degradation, but it does not prevent fork collapse

114 s and show that codepletion of RFWD3 rescues fork degradation, collapse, and cell sensitivity upon re

115 ould otherwise promote pathological reversed fork degradation.

116 ucture at 3.3 angstrom of human CMG bound to fork DNA and the ATP-analogue ATPgammaS.

117 g-strand DNA polymerase from the replication fork DNA helicase, and 2) on the damaged template, nasce

118 he AND-1 trimer is closely positioned to the fork DNA while its CIP (Ctf4-interacting peptide)-bindin

119 domain likely helps to position Bax1 at the forked DNA allowing the nuclease domain to incise one ar

120 re we report the cryo-EM structure of CMG on forked DNA at 3.9 angstrom, revealing that parental DNA

121 s: in the absence of DNA and in complex with forked duplex DNAs before and after cleavage of the 5' s

122 Single-molecule assessment of replication fork dynamics in BRG1-deficient cells revealed increased

123 ion is a stochastic process with replication forks emanating from multiple replication origins.

124 When replication forks encounter G-quadruplexes, EXO1 resects the nascent

125 When replication forks encounter template DNA lesions, the lesion is simp

126 cktracking reestablishes productive helicase-fork engagement, underscoring the significance of plasti

127 In the absence of the fork remodeler HLTF, forks fail to slow following replication stress, but und

128 s recombination and protects DNA replication forks from attrition.

129 ocalize at stalled forks and protect stalled forks from degradation by the MRE11 nuclease.

130 yet the molecular mechanisms for protecting forks from degradation/collapse are not well understood.

131 also required to protect stalled replication forks from nucleolytic degradation during response to hy

132 BRCA proteins protect reversed forks from nucleolytic degradation, and their loss leads

133 FAM111A, but not SPRTN, protects replication forks from stalling at poly(ADP-ribose) polymerase 1 (PA

134 results suggest that HAT1 links replication fork function to the proper processing and assembly of n

135 rk position, body size, and weaponry of male forked fungus beetles Bolitotherus cornutus as they infl

136 actin polymerization and by knocking out the forked gene in the mosquito (Ae-Forked; a known actin-bu

137 enance and resolution of stalled replication forks genome-wide.

138 nine recognition, we found that the arginine fork geometry was more consistent with the experimental

139 DNA phosphatase activities of PNKP, and the fork-head associated (FHA) domain that interacts with th

140 elicase with template DNA at the replication fork impairs its helicase activity, which is alleviated

141 chemists should feel comfortable taking this fork in the road, just as carbohydrate chemists should t

142 s, pol IV is rarely found at the replication fork in vivo.

143 lytic degradation of stalled DNA replication forks in a manner similar to that of cells lacking BRCA1

144 Stalled forks in BRCA2-deficient cells accumulate phosphorylated

145 novel mechanism by which RFWD3 destabilizes forks in BRCA2-deficient cells.

146 cessing of postreplication gaps or regressed forks in Escherichia coli.

147 hydroxyurea (HU)-induced stalled replication forks in the setting of BRCA1 deficiency.

148 show that ISG15 localizes at the replication forks, in complex with PCNA and the nascent DNA, where i

149 Mus81 from cleaving the stalled replication fork inappropriately.

150 ent maturation, PCNA-ubiquitination protects fork integrity and promotes the resistance of BRCA-defic

151 Protecting replication fork integrity during DNA replication is essential for m

152 P as a critical regulator of DNA replication fork integrity, which, when compromised, may predispose

153 with un-replicated DNAs ahead of replication forks into cohesive structures behind them, or from nucl

154 Stabilization of stalled replication forks is a prominent mechanism of PARP (Poly(ADP-ribose)

155 x mechanism, where dysfunctional replication forks lead to recruitment of error-prone polymerases.

156 ktracking, which interferes with replication forks, leading to DNA double-stranded breaks and genomic

157 DNA replication stress can stall replication forks, leading to genome instability.

158 eficiency increases MRE11 binding to stalled forks, leading to nascent-strand degradation at reversed

159 mature Australasian white sharks (147-350 cm fork length) with both acoustic and satellite transmitte

160 1-BARD1 functions in DNA repair, replication fork maintenance and tumour suppression, and its therape

161 seH, which were enriched for DNA replication fork maintenance factors including the MRE11-RAD50-NBS1

162 of chromosome damage repair and replication fork maintenance.

163 a protein hub central to DNA replication and fork management.

164 his remarkable plasticity of the replication fork may determine the outcome of replication stress in

165 When converging replication forks meet during replication termination, the CMG (Cdc4

166 Nearly 30 years ago, a theoretical arginine fork model was posited to account for the specificity be

167 as been proposed that at stalled replication forks, monoubiquitinated-FANCD2 serves to recruit DNA re

168 ss, it initiates checkpoint signaling at the forks necessary for maintaining genome stability and cel

169 teracting BaPif1 molecules are bound to each fork of the partially unwound dsDNA, and interact with t

170 unknown whether they activate HR at stalled forks or behind ongoing forks.

171 uch as those formed at collapsed replication forks or eroded telomeres.

172 cA-independent template switching at stalled forks or postreplication gaps.

173 rids within coding regions, independently of fork orientation.

174 arboxylation was found to follow a complex, "forked" pathway, which was confirmed by deuterium incorp

175 These data indicate that fork pausing at the TTS of highly expressed genes contai

176 ractions important for efficient replication fork pausing.

177 e correct metabolism of arrested replication forks, phenotype reminiscent of defective homologous rec

178 recent data on the relevance of replication fork plasticity to human health, covering its role in tu

179 regions, end resection, stalled replication fork processing, and mitochondrial genome maintenance.

180 nd RPA facilitate HR and promote replication fork progression and cellular viability in response to t

181 A proximal to these structures to facilitate fork progression and faithful replication.

182 relevant, as HAT1 loss decreased replication fork progression and increased replication fork stalling

183 ess response, promoting telomere replication fork progression and restart of stalled telomere replica

184 iciency, knockdown of SDE2 leads to impaired fork progression and stalled fork recovery, along with a

185 -deficient cells compromises DNA replication fork progression as well.

186 ctivities during replication stress leads to fork progression defects and activation of the Rad53 che

187 rate can be explained by laggard replication fork progression near the terminus region of the right r

188 moderate dependence on ATAD2 for replication fork progression was noted only for hdac2 cells overexpr

189 , no substantial perturbation of replication fork progression was observed, but rather mitotic progre

190 in HCT116 cells to pretumoral levels impeded fork progression without affecting checkpoint signaling.

191 o 3D chromatin organization, DNA replication fork progression, and DNA double-strand break (DSB) repa

192 polymerase uncoupling and impede replication fork progression, but the details of how uncoupled forks

193 solved, RNA-DNA hybrids can slow replication fork progression, cause DNA breaks, and increase mutagen

194 DNA damage tolerance pathways assist fork progression, promoting replication fork reversal, t

195 interferon-beta, accelerate DNA replication fork progression, resulting in extensive DNA damage and

196 gth Mdm4 was able to support DNA replication fork progression.

197 s (head-on) had little impact on replication fork progression.

198 f DNA unwinding and synthesis at replication forks promotes efficient and faithful replication of chr

199 defects in homologous recombination (HR) or fork protection (FP) do not.

200 hat PDS5 proteins participate in replication fork protection and also provide insights into how cohes

201 repair, pointing to a different mechanism of fork protection at different DNA lesions.

202 h CMG, including Ctf4 and the heterotrimeric fork protection complex (Csm3/Tof1 and Mrc1), which has

203 ication stress by regulating the replication fork protection complex (FPC).

204 EM) structures comprising CMG, Ctf4, and the fork protection complex at a replication fork.

205 Here, we show that a core component of the fork protection complex in the eukaryotic replisome, Tim

206 We propose that TIM-mediated fork protection may represent a way to cooperate with BR

207 nsitivity to PARPi by overcoming replication fork protection.

208 ngs identify the CST complex as an important fork protector that preserves genome integrity under rep

209 down-regulation restored normal replication fork rates in PDS5-deficient cells, suggesting that chro

210 ' to promote resumption of rapid replication fork rates, despite lesion bypass occurring uncoupled fr

211 eract with the excluded DNA strand stimulate fork rates.

212 slower compared to their in vivo replication fork rates.

213 ads to impaired fork progression and stalled fork recovery, along with a failure to activate CHK1 pho

214 eplication collisions, promoting replication fork recovery, and enforcing a G2/M cell-cycle arrest.

215 ATRX was recently implicated in replication fork recovery; however, the underlying mechanism(s) rema

216 bsence of SSB, PriA binds exclusively to the fork regions of the DNA substrates.

217 talling in mitochondria leads to replication fork regression and mtDNA double-strand breaks.

218 In the absence of the fork remodeler HLTF, forks fail to slow following replic

219 Our findings suggest that HLTF promotes fork remodeling, preventing other mechanisms of replicat

220 ay function upstream of BRCA2 in the stalled fork repair pathway.

221 egradation might not be sufficient to ensure fork repair.

222 cc2-dependent de novo loading at replication forks requires the Ctf18-RFC complex.

223 eria, the restart of stalled DNA replication forks requires the DNA helicase PriA.

224 Our observations have implications for both fork restart and the division of labor during leading-st

225 replication-stress signaling and replication-fork restart factors.

226 acting protein (CtIP) to promote replication fork restart while suppressing new origin firing.

227 CtIP and promote MRE11 exonuclease-dependent fork restart while suppressing the firing of new replica

228 PHF8 are required for efficient replication fork restart.

229 Gap suppression by either restoration of fork restraint or gap filling conferred therapy resistan

230 of BRCA2-deficient tumors, stabilize stalled forks, resulting in PARPi resistance in BRCA-deficient c

231 eneralizable to other conditions of impaired fork reversal (e.g., SMARCAL1 loss or PARP inhibition) a

232 te that HLTF-deficient cells fail to undergo fork reversal in vivo and rely on the primase-polymerase

233 s (SMARCAL1, ZRANB3, or HLTF), implicated in fork reversal, are not an integral component of the ICL

234 sist fork progression, promoting replication fork reversal, translesion DNA synthesis (TLS), and repr

235 accumulation of ssDNA gaps while suppressing fork reversal.

236 RCAL1, suggesting that it depends on stalled fork reversal.

237 topological stress inhibits DNA replication fork (RF) progression and contributes to DNA replication

238 eficient cells protected stalled replication forks (RFs).

239 and the recovery of stalled DNA replication forks (RFs).

240 , a piece of glass tubing bent into a tuning-fork shape and filled with any desired fluid.

241 overcoming protein obstacles to replication forks, shedding light on cellular responses to anti-canc

242 mma-H2AX on chromatin and global replication fork slowdown.

243 PI3K/mTORi decelerated fork speed by promoting new origin firing via increased

244 An increase in fork speed does not induce replication stress directly,

245 ication rate occur mainly through changes in fork speed without affecting the number of active forks.

246 romatid cohesion and reduced DNA replication fork speed.

247 By separating the role of Tof1 in DRC from fork stabilisation and coupling, we show that Tof1 has d

248 istone acetylation as critical regulators of fork stability and PARPi responses in BRCA-deficient cel

249 Epigenetic mechanisms of replication fork stability are emerging but remain poorly understood

250 e RFWD3 as an essential modulator of stalled fork stability in BRCA2-deficient cells and show that co

251 , Sld3, and Dun1, substrates contributing to fork stability, induces spindle extension.

252 scriptional activity compromises replication fork stability, potentially leading to gene mutations.

253 tination is a critical event for replication fork stabilization by the Fanconi anemia (FA) DNA repair

254 elicase activity, suggesting a mechanism for fork stabilization by the replication checkpoint.

255 The mechanism of Rad53-dependent fork stabilization is not known.

256 esent a way to cooperate with BRCA-dependent fork stabilization.

257 n recombinational DNA repair and replication fork stabilization.

258 We found that most converging forks stall at a very late stage, indicating a role for

259 of H. pylori, is accompanied by replication fork stalling and can be observed also in primary cells

260 ls specifically sensitive to the replication fork stalling and collapse caused by methyl methanesulfo

261 as mtDNA deletions initiated by replication fork stalling during strand displacement mtDNA synthesis

262 One way to prevent replication fork stalling is through the recruitment of specialized

263 locks, most genome-destabilizing replication fork stalling likely occurs because of proteins bound to

264 and polymerase, Ctf18-RFC can rapidly signal fork stalling to activate the S phase checkpoint.

265 under these conditions does not result from fork stalling, but rather occurs at gaps formed by PrimP

266 cells, POLE suppression leads to replication fork stalling, DNA damage, and a senescence-like state o

267 te with synergistic increases in replication fork stalling, double-strand breaks, and apoptosis.

268 n stress, possibly by increasing replication fork stalling, providing a molecular mechanism for the d

269 In response to DNA damage or replication fork stalling, the basal activity of Mec1(ATR) is stimul

270 n fork progression and increased replication fork stalling.

271 nsient, but can be stabilized by replication fork stalling.

272 mediated genome instability, and replication fork stalling.

273 f ICL repair is activated when a replication fork stalls at an ICL(2); this triggers monoubiquitinati

274 omes imply that most cancers suffer frequent fork stalls that are reduced by the HJ removers EME1 and

275 '-tailed duplexes, suggesting that it is the fork structure that plays an essential role in PriA's se

276 unhooking interstrand cross-links (ICLs) at fork structures.

277 sence of SSB, PriA binds preferentially to a fork substrate with a gap in the leading strand.

278 d SSB loads PriA onto the duplex DNA arms of forks, suggesting a remodeling of PriA by SSB.

279 iation driven by a migratory drop-off in the fork-tailed flycatcher (Tyrannus savana) resulting in re

280 s revealed four distinct classes of arginine forks that we have defined using a rigorous but flexible

281 a recurrent structural motif, the "arginine fork", that codifies arginine readout of cognate backbon

282 unlike the processing at HU-induced stalled forks, the function of the SNF2 translocases (SMARCAL1,

283 ized histones in the wake of the replication fork through the activity of the replication-coupled chr

284 tion requires the progression of replication forks through DNA damage, actively transcribed regions,

285 which stably associates with DNA replication forks throughout elongation.

286 li by monitoring the location of replication forks throughout on average >500 cell cycles per knockdo

287 that CST inhibits MRE11 binding to reversed forks, thus antagonizing excessive nascent-strand degrad

288 ct role of Nup1 in the relocation of stalled forks to NPCs and restriction of error-prone recombinati

289 yeast, we report that relocation of arrested forks to NPCs occurred after Rad51 loading and its enzym

290 The E3 SUMO ligase Pli1 acts at arrested forks to safeguard integrity of nascent strands and gene

291 romatin components at individual replication forks undergoing DNA replication.

292 ognize and remodel abandoned DNA replication forks, unwind DNA in the 3'-to-5' direction, and facilit

293 o showed that the progression of replication forks was altered in ORSCs from hair follicles of HS pat

294 -directionally oriented with the replication fork were transient blockages, whereas those oriented he

295 in the absence of HAT1, stalled replication forks were unstable, and newly synthesized DNA became su

296 X and FANCD2 localize to stalled replication forks where they cooperate to recruit CtIP and promote M

297 s by acetylating H4K8 at stalled replication forks, which recruits MRE11 and EXO1.

298 location, direction and speed of replication forks with high resolution.

299 ons between PriA and stalled DNA replication forks with or without SSB.

300 findings prompted us to search for arginine forks within experimental protein-RNA structures retriev