2015
DOI: 10.1038/nsmb.2956
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DNA interstrand cross-link repair requires replication-fork convergence

Abstract: DNA interstrand cross-links (ICLs) prevent strand separation during DNA replication and transcription and are therefore extremely cytotoxic. In metazoans, a major pathway of ICL repair is coupled to DNA replication and requires the Fanconi anemia pathway. In most current models, collision of a single DNA replication fork with an ICL is sufficient to initiate repair. In contrast, we show here that in Xenopus egg extracts, two DNA replication forks must converge on an ICL to trigger repair. When only one fork re… Show more

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Cited by 138 publications
(125 citation statements)
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“…CMG complexes from both replication forks unload from both leading strands, as previously described (Long et al , 2014; Zhang et al , 2015) which enables one nascent leading strand to gradually progresses to 1 nt from the ICL (“0” position; step b‐ii) as previously described (Raschle et al , 2008; Zhang et al , 2015). The structure that arises at this stage is inhibitory for XPF‐ERCC1.…”
Section: Discussionmentioning
confidence: 95%
See 2 more Smart Citations
“…CMG complexes from both replication forks unload from both leading strands, as previously described (Long et al , 2014; Zhang et al , 2015) which enables one nascent leading strand to gradually progresses to 1 nt from the ICL (“0” position; step b‐ii) as previously described (Raschle et al , 2008; Zhang et al , 2015). The structure that arises at this stage is inhibitory for XPF‐ERCC1.…”
Section: Discussionmentioning
confidence: 95%
“…A number of major breakthroughs in our understanding of replication‐coupled ICL repair have recently emerged from a cell‐free replication‐coupled repair system in X enopus laevis egg extracts (Raschle et al , 2008; Klein Douwel et al , 2014; Zhang et al , 2015). ICL repair is triggered by the convergence of dual replication forks at an ICL, and moreover, this convergence is a near‐absolute requirement for the initiation of ICL repair (Zhang et al , 2015).…”
Section: Discussionmentioning
confidence: 99%
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“…Using a Xenopus egg extract‐based assay, we and others have recently elucidated a molecular mechanism of replication‐coupled ICL repair (Fig EV1; Räschle et al , 2008). This mechanism requires the convergence of two replication forks at an ICL during DNA replication (Zhang et al , 2015). Both forks initially stall 20–40 nucleotides from the crosslink followed by CMG helicase unloading allowing one fork to approach to within 1 nucleotide of the crosslink (Räschle et al , 2008; Fu et al , 2011; Long et al , 2011).…”
Section: Introductionmentioning
confidence: 99%
“…One such mechanism could entail the stabilization of an arrested replication fork until the arrival of the converging second fork. 32 To determine whether increased spatial separation of the 2 forks arrested at Tus/Ter affects HR, we studied the impact of extended Ter arrays on the induction of HR at Tus/ Ter-stalled forks, using defined reporters targeted, in parallel, to the ROSA26 locus of mouse embryonic stem (ES) cells. Our results suggest that coordination between the 2 arrested converging forks influences the quality of HR at the Tus/Ter replication fork barrier.…”
Section: Introductionmentioning
confidence: 99%