Overlapping mechanisms promote postsynaptic RAD-51 filament disassembly during meiotic double-strand break repair.
Homologous recombination (HR) is essential for repair of meiotic DNA double-strand breaks (DSBs). Although the mechanisms of RAD-51-DNA filament assembly and strand exchange are well characterized, the subsequent steps of HR are less well defined. Here, we describe a synthetic lethal interaction between the C. elegans helicase helq-1 and RAD-51 paralog rfs-1, which results in a block to meiotic DSB repair after strand invasion. Whereas RAD-51-ssDNA filaments assemble at meiotic DSBs with normal kinetics in helq-1, rfs-1 double mutants, persistence of RAD-51 foci and genetic interactions with rtel-1 suggest a failure to disassemble RAD-51 from strand invasion intermediates. Indeed, purified HELQ-1 and RFS-1 independently bind to and promote the disassembly of RAD-51 from double-stranded, but not single-stranded, DNA filaments via distinct mechanisms in vitro. These results indicate that two compensating activities are required to promote postsynaptic RAD-51 filament disassembly, which are collectively essential for completion of meiotic DSB repair.
Ward
Jordan D
JD
DNA Damage Response Laboratory, Cancer Research UK, Clare Hall Laboratories, South Mimms EN6 3LD, UK.
Muzzini
Diego M
DM
Petalcorin
Mark I R
MI
Martinez-Perez
Enrique
E
Martin
Julie S
JS
Plevani
Paolo
P
Cassata
Giuseppe
G
Marini
Federica
F
Boulton
Simon J
SJ
D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D053903:DNA Breaks, Double-Stranded; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D018509:DNA, Helminth / Q000378:metabolism; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008540:Meiosis; D009154:Mutation; D051135:Rad51 Recombinase / Q000378:metabolism*; D011995:Recombination, Genetic
D029742:Caenorhabditis elegans Proteins; D018509:DNA, Helminth; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; C000602003:RFS-1 protein, C elegans; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans; C547400:HELQ-1 protein, C elegans; D004265:DNA Helicases