RRC ID 59358
Author Janisiw E, Dello Stritto MR, Jantsch V, Silva N.
Title BRCA1-BARD1 associate with the synaptonemal complex and pro-crossover factors and influence RAD-51 dynamics during Caenorhabditis elegans meiosis.
Journal PLoS Genet
Abstract 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.
Volume 14(11)
Pages e1007653
Published 2018-11-1
DOI 10.1371/journal.pgen.1007653
PMID 30383754
PMC PMC6211622
MeSH Animals BRCA1 Protein / genetics BRCA1 Protein / metabolism* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Chromosome Pairing Germ Cells / metabolism Meiosis* / genetics Multiprotein Complexes / metabolism Protein Binding Protein Transport Rad51 Recombinase / genetics Rad51 Recombinase / metabolism* Synaptonemal Complex / metabolism*
IF 5.224
Times Cited 8
C.elegans tm1145 tm3298 tm611 tm574