RRC ID 3643
Author Ward JD, Barber LJ, Petalcorin MI, Yanowitz J, Boulton SJ.
Title Replication blocking lesions present a unique substrate for homologous recombination.
Journal EMBO J.
Abstract 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.
Volume 26(14)
Pages 3384-96
Published 2007-7-25
DOI 10.1038/sj.emboj.7601766
PII 7601766
PMID 17611606
PMC PMC1933397
MeSH Animals Caenorhabditis elegans / cytology Caenorhabditis elegans / genetics* Caenorhabditis elegans / radiation effects Caenorhabditis elegans Proteins / metabolism Crossing Over, Genetic / radiation effects DNA Breaks, Double-Stranded / radiation effects DNA Damage* DNA Repair / radiation effects DNA Replication* / radiation effects Gene Deletion Meiosis / radiation effects Mitosis / radiation effects Poly C Poly G Protein Binding / radiation effects Rad51 Recombinase / metabolism Recombination, Genetic* / radiation effects Substrate Specificity / radiation effects Suppression, Genetic / radiation effects Ultraviolet Rays
IF 10.557
Times Cited 48
C.elegans tm1145 tm1937 tm853 tm1086