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Replication blocking lesions present a unique substrate for homologous recombination
Author(s) -
Ward Jordan D,
Barber Louise J,
Petalcorin Mark IR,
Yanowitz Judith,
Boulton Simon J
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601766
Subject(s) - biology , homologous recombination , replication (statistics) , blocking (statistics) , homologous chromosome , recombination , genetics , dna , gene , virology , computer science , computer network
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.