title: Pseudosynapsis and decreased stringency of meiotic repair pathway choice on the hemizygous sex chromosome of Caenorhabditis elegans males.
abstract: During meiosis, accurate chromosome segregation relies on homology to mediate chromosome pairing, synapsis, and crossover recombination. Crossovers are dependent upon formation and repair of double-strand breaks (DSBs) by homologous recombination (HR). In males of many species, sex chromosomes are largely hemizygous, yet DSBs are induced along nonhomologous regions. Here we analyzed the genetic requirements for meiotic DSB repair on the completely hemizygous X chromosome of Caenorhabditis elegans males. Our data reveal that the kinetics of DSB formation, chromosome pairing, and synapsis are tightly linked in the male germ line. Moreover, DSB induction on the X is concomitant with a brief period of pseudosynapsis that may allow X sister chromatids to masquerade as homologs. Consistent with this, neither meiotic kleisins nor the SMC-5/6 complex are essential for DSB repair on the X. Furthermore, early processing of X DSBs is dependent on the CtIP/Sae2 homolog COM-1, suggesting that as with paired chromosomes, HR is the preferred pathway. In contrast, the X chromosome is refractory to feedback mechanisms that ensure crossover formation on autosomes. Surprisingly, neither RAD-54 nor BRC-2 are essential for DSB repair on the X, suggesting that unlike autosomes, the X is competent for repair in the absence of HR. When both RAD-54 and the structure-specific nuclease XPF-1 are abrogated, X DSBs persist, suggesting that single-strand annealing is engaged in the absence of HR. Our findings indicate that alteration in sister chromatid interactions and flexibility in DSB repair pathway choice accommodate hemizygosity on sex chromosomes.
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
authors.forename: Paula M
authors.initials: PM
authors.lastname: Checchi
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
authors.forename: Katherine S
authors.initials: KS
authors.lastname: Lawrence
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
authors.forename: Mike V
authors.initials: MV
authors.lastname: Van
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616.
authors.forename: Braden J
authors.initials: BJ
authors.lastname: Larson
authors.affiliation: Department of Molecular and Cellular Biology, University of California, Davis, California 95616 jengebrecht@ucdavis.edu.
authors.forename: JoAnne
authors.initials: J
authors.lastname: Engebrecht
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics; D023902:Chromosome Pairing; D020090:Chromosome Segregation; D003434:Crossing Over, Genetic; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D008297:Male; D008540:Meiosis; D009687:Nuclear Proteins / Q000235:genetics; D051135:Rad51 Recombinase / Q000235:genetics; D014960:X Chromosome / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D009687:Nuclear Proteins; C569962:SYP-1 protein, C elegans; D051135:Rad51 Recombinase; C495148:rad-51 protein, C elegans
keywords: double strand breaks (DSBs); genetics of sex; homologous recombination; meiosis; sex chromosome; synapsis