BRC-1 acts in the inter-sister pathway of meiotic double-strand break repair.
The breast and ovarian cancer susceptibility protein BRCA1 is evolutionarily conserved and functions in DNA double-strand break (DSB) repair through homologous recombination, but its role in meiosis is poorly understood. By using genetic analysis, we investigated the role of the Caenorhabditis elegans BRCA1 orthologue (brc-1) during meiotic prophase. The null mutant in the brc-1 gene is viable, fertile and shows the wild-type complement of six bivalents in most diakinetic nuclei, which is indicative of successful crossover recombination. However, brc-1 mutants show an abnormal increase in apoptosis and RAD-51 foci at pachytene that are abolished by loss of spo-11 function, suggesting a defect in meiosis rather than during premeiotic DNA replication. In genetic backgrounds in which chiasma formation is abrogated, such as him-14/MSH4 and syp-2, loss of brc-1 leads to chromosome fragmentation suggesting that brc-1 is dispensable for crossing over but essential for DSB repair through inter-sister recombination.
Adamo
Adele
A
Institute of Genetics and Biophysics Adriano Buzzati-Traverso CNR, Via Pietro Castellino 111, Napoli 80131, Italy.
Montemauri
Paolo
P
Silva
Nicola
N
Ward
Jordan D
JD
Boulton
Simon J
SJ
La Volpe
Adriana
A
D000818:Animals; D017209:Apoptosis; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000201:enzymology; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D020964:Embryo Loss; D004706:Endodeoxyribonucleases; D004950:Esterases / Q000378:metabolism; D007211:Indoles; D008540:Meiosis; D049469:Meiotic Prophase I; D009154:Mutation / Q000235:genetics; D051135:Rad51 Recombinase / Q000378:metabolism; D000099257:Meiotic Recombination Protein SPO11
D029742:Caenorhabditis elegans Proteins; D004706:Endodeoxyribonucleases; D004950:Esterases; D007211:Indoles; D051135:Rad51 Recombinase; D000099257:Meiotic Recombination Protein SPO11; C528463:BRC-1 protein, C elegans; C007293:DAPI