title: Interplay between structure-specific endonucleases for crossover control during Caenorhabditis elegans meiosis.
abstract: The number and distribution of crossover events are tightly regulated at prophase of meiosis I. The resolution of Holliday junctions by structure-specific endonucleases, including MUS-81, SLX-1, XPF-1 and GEN-1, is one of the main mechanisms proposed for crossover formation. However, how these nucleases coordinately resolve Holliday junctions is still unclear. Here we identify both the functional overlap and differences between these four nucleases regarding their roles in crossover formation and control in the Caenorhabditis elegans germline. We show that MUS-81, XPF-1 and SLX-1, but not GEN-1, can bind to HIM-18/SLX4, a key scaffold for nucleases. Analysis of synthetic mitotic defects revealed that MUS-81 and SLX-1, but not XPF-1 and GEN-1, have overlapping roles with the Bloom syndrome helicase ortholog, HIM-6, supporting their in vivo roles in processing recombination intermediates. Taking advantage of the ease of genetic analysis and high-resolution imaging afforded by C. elegans, we examined crossover designation, frequency, distribution and chromosomal morphology in single, double, triple and quadruple mutants of the structure-specific endonucleases. This revealed that XPF-1 functions redundantly with MUS-81 and SLX-1 in executing crossover formation during meiotic double-strand break repair. Analysis of crossover distribution revealed that SLX-1 is required for crossover suppression at the center region of the autosomes. Finally, analysis of chromosome morphology in oocytes at late meiosis I stages uncovered that SLX-1 and XPF-1 promote meiotic chromosomal stability by preventing formation of chromosomal abnormalities. We propose a model in which coordinate action between structure-specific nucleases at different chromosome domains, namely MUS-81, SLX-1 and XPF-1 at the arms and SLX-1 at the center region, exerts positive and negative regulatory roles, respectively, for crossover control during C. elegans meiosis.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Takamune T
authors.initials: TT
authors.lastname: Saito
authors.forename: Doris Y
authors.initials: DY
authors.lastname: Lui
authors.forename: Hyun-Min
authors.initials: HM
authors.lastname: Kim
authors.forename: Katherine
authors.initials: K
authors.lastname: Meyer
authors.forename: Monica P
authors.initials: MP
authors.lastname: Colaiácovo
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D020090:Chromosome Segregation / Q000235:genetics; D003434:Crossing Over, Genetic; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism*; D045566:DNA, Cruciform / Q000235:genetics; D003851:Deoxyribonucleases / Q000235:genetics* / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases / Q000235:genetics*; D008540:Meiosis / Q000235:genetics*; D009865:Oocytes / Q000378:metabolism; D011485:Protein Binding; D011995:Recombination, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; D045566:DNA, Cruciform; C487047:HIM-6 protein, C elegans; D003851:Deoxyribonucleases; D004706:Endodeoxyribonucleases; D004720:Endonucleases; C575962:HIM-18 protein, C elegans; C585453:MUS-81 protein, C elegans; C547401:SLX-1 protein, C elegans; C547402:XPF-1 protein, C elegans; D004265:DNA Helicases