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Replication blocking lesions present a unique substrate for homologous recombination.
- Source :
-
The EMBO journal [EMBO J] 2007 Jul 25; Vol. 26 (14), pp. 3384-96. Date of Electronic Publication: 2007 Jul 05. - Publication Year :
- 2007
-
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.
- Subjects :
- Animals
Caenorhabditis elegans cytology
Caenorhabditis elegans radiation effects
Caenorhabditis elegans Proteins metabolism
Crossing Over, Genetic radiation effects
DNA Breaks, Double-Stranded radiation effects
DNA Repair radiation effects
Gene Deletion
Meiosis radiation effects
Mitosis radiation effects
Poly C
Poly G
Protein Binding radiation effects
Rad51 Recombinase metabolism
Substrate Specificity radiation effects
Suppression, Genetic radiation effects
Ultraviolet Rays
Caenorhabditis elegans genetics
DNA Damage
DNA Replication radiation effects
Recombination, Genetic radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 0261-4189
- Volume :
- 26
- Issue :
- 14
- Database :
- MEDLINE
- Journal :
- The EMBO journal
- Publication Type :
- Academic Journal
- Accession number :
- 17611606
- Full Text :
- https://doi.org/10.1038/sj.emboj.7601766