title: COSA-1 reveals robust homeostasis and separable licensing and reinforcement steps governing meiotic crossovers.
abstract: Crossovers (COs) between homologous chromosomes ensure their faithful segregation during meiosis. We identify C. elegans COSA-1, a cyclin-related protein conserved in metazoa, as a key component required to convert meiotic double-strand breaks (DSBs) into COs. During late meiotic prophase, COSA-1 localizes to foci that correspond to the single CO site on each homolog pair and indicate sites of eventual concentration of other conserved CO proteins. Chromosomes gain and lose competence to load CO proteins during meiotic progression, with competence to load COSA-1 requiring prior licensing. Our data further suggest a self-reinforcing mechanism maintaining CO designation. Modeling of a nonlinear dose-response relationship between IR-induced DSBs and COSA-1 foci reveals efficient conversion of DSBs into COs when DSBs are limiting and a robust capacity to limit cytologically differentiated CO sites when DSBs are in excess. COSA-1 foci serve as a unique live cell readout for investigating CO formation and CO interference.
authors.affiliation: Department of Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: Rayka
authors.initials: R
authors.lastname: Yokoo
authors.forename: Karl A
authors.initials: KA
authors.lastname: Zawadzki
authors.forename: Kentaro
authors.initials: K
authors.lastname: Nabeshima
authors.forename: Melanie
authors.initials: M
authors.lastname: Drake
authors.forename: Swathi
authors.initials: S
authors.lastname: Arur
authors.forename: Anne M
authors.initials: AM
authors.lastname: Villeneuve
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002875:Chromosomes / Q000378:metabolism; D003434:Crossing Over, Genetic; D016213:Cyclins / Q000235:genetics / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008540:Meiosis; D008958:Models, Molecular; D009154:Mutation
chemical_list: C584819:COSA-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D016213:Cyclins; D004268:DNA-Binding Proteins