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| Subject Categories: Genome Stability & Dynamics |
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| The EMBO Journal
(2007) 26, 3384–3396, doi:10.1038/sj.emboj.7601766 Published online 5 July 2007 |
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| Replication blocking lesions present a unique substrate for homologous recombination |
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| Jordan D Ward1, Louise J Barber1, Mark IR Petalcorin1, Judith Yanowitz2 and Simon J Boulton1 |
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1 DNA Damage Response Laboratory, Cancer Research UK, The London Research Institute, Clare Hall Laboratories, South Mimms, Herts, UK 2 Carnegie Institution, Department of Embryology, Baltimore, MD, USA To whom correspondence should be addressed Simon J Boulton, DNA Damage Response Laboratory, Cancer Research UK, The London Research Institute, Clare Hall Laboratories, South Mimms, Herts EN6 3LD, UK. Tel.: +44 1707 625774; Fax: +44 2072 693801; E-mail: simon.boulton@cancer.org.uk Received 4 April 2007; Accepted 24 May 2007; Published online 5 July 2007. |
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| Abstract |
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| Homologous recombination (HR) plays a critical role in the restart of blocked replication forks, but how this is achieved remains poorly understood. We show that mutants in the single Rad51 paralog in Caenorhabditis elegans, rfs-1, permit discrimination between HR substrates generated at DNA double-strand breaks (DSBs), or following replication fork collapse from HR substrates assembled at replication fork barriers (RFBs). Unexpectedly, RFS-1 is dispensable for RAD-51 recruitment to meiotic and ionizing radiation (IR)-induced DSBs and following replication fork collapse, yet, is essential for RAD-51 recruitment to RFBs formed by DNA crosslinking agents and other replication blocking lesions. Deletion of rfs-1 also suppresses the accumulation of toxic HR intermediates in him-6; top-3 mutants and accelerates deletion formation at presumed endogenous RFBs formed by poly G/C tracts in the absence of DOG-1. These data suggest that RFS-1 is not a general mediator of HR-dependent DSB repair, but acts specifically to promote HR at RFBs. HR substrates generated at conventional DSBs or following replication fork collapse are therefore intrinsically different from those produced during normal repair of blocked replication forks. |
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| Keywords: C. elegans , homologous recombination, ICL repair, Rad51 paralogs, replication fork barriers |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHThe RNA acetyltransferase driven by ATP hydrolysis synthesizes N 4 -acetylcytidine of tRNA anticodon The EMBO Journal Article (20 Aug 2008) Replication blocking lesions present a unique substrate for homologous recombination The EMBO Journal Article The EMBO Journal Article (21 Dec 2005) The EMBO Journal Article |
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