title: REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand break formation in Caenorhabditis elegans.
abstract: The Caenorhabditis elegans gene rec-1 was the first genetic locus identified in metazoa to affect the distribution of meiotic crossovers along the chromosome. We report that rec-1 encodes a distant paralog of HIM-5, which was discovered by whole-genome sequencing and confirmed by multiple genome-edited alleles. REC-1 is phosphorylated by cyclin-dependent kinase (CDK) in vitro, and mutation of the CDK consensus sites in REC-1 compromises meiotic crossover distribution in vivo. Unexpectedly, rec-1; him-5 double mutants are synthetic-lethal due to a defect in meiotic double-strand break formation. Thus, we uncovered an unexpected robustness to meiotic DSB formation and crossover positioning that is executed by HIM-5 and REC-1 and regulated by phosphorylation.
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
authors.forename: George
authors.initials: G
authors.lastname: Chung
authors.affiliation: Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
authors.forename: Ann M
authors.initials: AM
authors.lastname: Rose
authors.affiliation: DNA Damage Response Laboratory, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom; Clare Hall Laboratories, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom;
authors.forename: Mark I R
authors.initials: MI
authors.lastname: Petalcorin
authors.affiliation: DNA Damage Response Laboratory, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom; Clare Hall Laboratories, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom;
authors.forename: Julie S
authors.initials: JS
authors.lastname: Martin
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA;
authors.forename: Zebulin
authors.initials: Z
authors.lastname: Kessler
authors.affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.
authors.forename: Luis
authors.initials: L
authors.lastname: Sanchez-Pulido
authors.affiliation: Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom.
authors.forename: Chris P
authors.initials: CP
authors.lastname: Ponting
authors.affiliation: Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA;
authors.forename: Judith L
authors.initials: JL
authors.lastname: Yanowitz
authors.affiliation: DNA Damage Response Laboratory, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom; Clare Hall Laboratories, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom;
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Boulton
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D003434:Crossing Over, Genetic / Q000235:genetics*; D053903:DNA Breaks, Double-Stranded; D008540:Meiosis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C000603413:HIM-5 protein, C elegans; C000603411:REC-1 protein, C elegans
keywords: HIM-5; REC-1; cyclin-dependent kinase; meiosis; meiotic crossover distribution