BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis

• Published in: PLoS genetics Vol. 14; no. 11; p. e1007653
• Main Authors: Janisiw, Eva, Dello Stritto, Maria Rosaria, Jantsch, Verena, Silva, Nicola
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01-11-2018; Public Library of Science (PLoS)
• Subjects: Animals; Apoptosis; Biology; Biology and Life Sciences; BRCA1 protein; BRCA1 Protein - genetics; BRCA1 Protein - metabolism; Breast; Breast cancer; Caenorhabditis elegans; Caenorhabditis elegans - genetics; Caenorhabditis elegans - metabolism; Caenorhabditis elegans Proteins - genetics; Caenorhabditis elegans Proteins - metabolism; Cell division; Chromosome Pairing; Chromosomes; Crossing over (Genetics); Deoxyribonucleic acid; Disease susceptibility; DNA; DNA damage; DNA repair; Double-strand break repair; Gametes; Gametogenesis; Genetic aspects; Genetics; Genomes; Germ Cells - metabolism; Ionizing radiation; Laboratories; Localization; Medicine and Health Sciences; Meiosis; Meiosis - genetics; Melanocyte stimulating hormone; Multiprotein Complexes - metabolism; Nematodes; Observations; Ovarian cancer; Parenting; Perutz, Max; Physiological aspects; Prophase; Protein Binding; Protein Transport; Proteins; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Recombinase; Recombination; Research and Analysis Methods; Synaptonemal complex; Synaptonemal Complex - metabolism; Worms; Austria
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1007653

During meiosis, the maternal and paternal homologous chromosomes must align along their entire length and recombine to achieve faithful segregation in the gametes. Meiotic recombination is accomplished through the formation of DNA double-strand breaks, a subset of which can mature into crossovers to link the parental homologous chromosomes and promote their segregation. Breast and ovarian cancer susceptibility protein BRCA1 and its heterodimeric partner BARD1 play a pivotal role in DNA repair in mitotic cells; however, their functions in gametogenesis are less well understood. Here we show that localization of BRC-1 and BRD-1 (Caenorhabditis elegans orthologues of BRCA1 and BARD1) is dynamic during meiotic prophase I; they ultimately becoming concentrated at regions surrounding the presumptive crossover sites, co-localizing with the pro-crossover factors COSA-1, MSH-5 and ZHP-3. The synaptonemal complex and PLK-2 activity are essential for recruitment of BRC-1 to chromosomes and its subsequent redistribution towards the short arm of the bivalent. BRC-1 and BRD-1 form in vivo complexes with the synaptonemal complex component SYP-3 and the crossover-promoting factor MSH-5. Furthermore, BRC-1 is essential for efficient stage-specific recruitment/stabilization of the RAD-51 recombinase to DNA damage sites when synapsis is impaired and upon induction of exogenous damage. Taken together, our data provide new insights into the localization and meiotic function of the BRC-1-BRD-1 complex and highlight its essential role in DNA double-strand break repair during gametogenesis.