2017
DOI: 10.1016/j.molcel.2017.11.022
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Replication Fork Reversal: Players and Guardians

Abstract: Summary Replication fork reversal is a rapidly emerging and remarkably frequent mechanism of fork stabilization in response to genotoxic insults. Here, we summarize recent findings that uncover key molecular determinants for reversed fork formation and describe how the homologous recombination factors BRCA1, BRCA2 and RAD51 protect these structures from extended nucleolytic degradation.

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Cited by 246 publications
(245 citation statements)
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“…In addition to unwinding, ssDNA can be generated by helicases or nuclease-mediated resection of the fork, particularly when it is regressed ( Figure S1A) (Quinet et al, 2017). To determine if stalled forks in TLK depleted cells were actively targeted by resection enzymes, we co-depleted or inhibited several candidate proteins, including MRE11, CTIP, SAMHD1 and the BLM helicase.…”
Section: Resultsmentioning
confidence: 99%
“…In addition to unwinding, ssDNA can be generated by helicases or nuclease-mediated resection of the fork, particularly when it is regressed ( Figure S1A) (Quinet et al, 2017). To determine if stalled forks in TLK depleted cells were actively targeted by resection enzymes, we co-depleted or inhibited several candidate proteins, including MRE11, CTIP, SAMHD1 and the BLM helicase.…”
Section: Resultsmentioning
confidence: 99%
“…Thus, we investigated if fork reversal is also required for nascent tract degradation in KR cells. Fork reversal depends on RAD51 and the translocases HLTF, ZRANB3, and SMARCAL1 (Cortez, 2019;Kolinjivadi et al, 2017;Mijic et al, 2017;Quinet et al, 2017;Taglialatela et al, 2017;Zellweger et al, 2015). Depletion of RAD51 restored nascent tract integrity in KR cells ( Figure 3A; Figure S3A), indicating that fork reversal by RAD51 is indeed a prerequisite for nascent strand degradation in KR cells as well.…”
Section: Nascent Tract Degradation In Pcna Ubiquitination-defective Cmentioning
confidence: 93%
“…In response to replication stress, forks can be reversed, which involves their processing into four-way junctions upon annealing of the complementary nascent strands. Fork reversal is thought to function as a protection mechanism against fork collapse by providing an opportunity to bypass the DNA injury by using the nascent strand of the intact sister chromatid as a temporary template for DNA synthesis (Bhat and Cortez, 2018;Cortez, 2019;Quinet et al, 2017). However, reversal can also render replication forks susceptible to nucleolytic processing.…”
Section: Introductionmentioning
confidence: 99%
“…CST antagonizes MRE11 degradation of nascent strand DNA at stalled forks In response to replication stalling, forks may reverse to stabilize stalled forks and promote restart (Quinet et al, 2017b). Reversed forks, if not protected properly, are attacked by nucleases such as MRE11, DNA2 and EXOI, causing excessive degradation of nascent strand DNA (Lemacon et al, 2017;Thangavel et al, 2015).…”
Section: Cst Localizes At Stalled Forksmentioning
confidence: 99%
“…This fork reversal mechanism has emerged as an important means for stabilizing stalled forks and resuming replication following replication perturbation. For this reason, the dynamics of reversed forks has been extensively studied (Neelsen & Lopes, 2015;Quinet et al, 2017b;Rickman & Smogorzewska, 2019). The formation of reversed forks is catalyzed by SMARCAL1, ZRANB3, FANCM, HLTF, FBH1, and perhaps others (Betous et al, 2012;Gari et al, 2008;Kile et al, 2015;Kolinjivadi et al, 2017;Taglialatela et al, 2017;Vujanovic et al, 2017), and also involves RAD51 .…”
Section: Introductionmentioning
confidence: 99%