title: Identification of DSB-1, a protein required for initiation of meiotic recombination in Caenorhabditis elegans, illuminates a crossover assurance checkpoint.
abstract: Meiotic recombination, an essential aspect of sexual reproduction, is initiated by programmed DNA double-strand breaks (DSBs). DSBs are catalyzed by the widely-conserved Spo11 enzyme; however, the activity of Spo11 is regulated by additional factors that are poorly conserved through evolution. To expand our understanding of meiotic regulation, we have characterized a novel gene, dsb-1, that is specifically required for meiotic DSB formation in the nematode Caenorhabditis elegans. DSB-1 localizes to chromosomes during early meiotic prophase, coincident with the timing of DSB formation. DSB-1 also promotes normal protein levels and chromosome localization of DSB-2, a paralogous protein that plays a related role in initiating recombination. Mutations that disrupt crossover formation result in prolonged DSB-1 association with chromosomes, suggesting that nuclei may remain in a DSB-permissive state. Extended DSB-1 localization is seen even in mutants with defects in early recombination steps, including spo-11, suggesting that the absence of crossover precursors triggers the extension. Strikingly, failure to form a crossover precursor on a single chromosome pair is sufficient to extend the localization of DSB-1 on all chromosomes in the same nucleus. Based on these observations we propose a model for crossover assurance that acts through DSB-1 to maintain a DSB-permissive state until all chromosome pairs acquire crossover precursors. This work identifies a novel component of the DSB machinery in C. elegans, and sheds light on an important pathway that regulates DSB formation for crossover assurance.
authors.affiliation: Department of Molecular and Cell Biology and California Institute for Quantitative Biosciences (QB3), University of California, Berkeley; Berkeley, California, United States of America.
authors.forename: Ericca L
authors.initials: EL
authors.lastname: Stamper
authors.forename: Stacia E
authors.initials: SE
authors.lastname: Rodenbusch
authors.forename: Simona
authors.initials: S
authors.lastname: Rosu
authors.forename: Julie
authors.initials: J
authors.lastname: Ahringer
authors.forename: Anne M
authors.initials: AM
authors.lastname: Villeneuve
authors.forename: Abby F
authors.initials: AF
authors.lastname: Dernburg
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D023902:Chromosome Pairing / Q000235:genetics; D020090:Chromosome Segregation / Q000235:genetics; D002875:Chromosomes / Q000378:metabolism; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D059765:Homologous Recombination / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D009154:Mutation
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C587165:DSB-1 protein, C elegans