REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand break formation in Caenorhabditis elegans

George Chung; Ann M. Rose; Mark I.R. Petalcorin; Julie S. Martin; Zebulin Kessler; Luis Sanchez-Pulido; Chris P. Ponting; Judith L. Yanowitz; Simon J. Boulton

doi:10.1101/gad.266056.115

REC-1 and HIM-5 distribute meiotic crossovers and function redundantly in meiotic double-strand break formation in Caenorhabditis elegans

¹Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada;
²DNA Damage Response Laboratory, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom;
³Clare Hall Laboratories, The Francis Crick Institute, South Mimms EN3 3LD, United Kingdom;
⁴Magee-Womens Research Institute, Department of Obstetrics, Gynecology, and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA;
⁵Medical Research Council Functional Genomics Unit, Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford OX1 3PT, United Kingdom

Corresponding authors: simon.boulton{at}crick.ac.uk, yanowitzjl{at}mwri.magee.edu

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.

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Footnotes

Supplemental material is available for this article.
Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.266056.115.
Freely available online through the Genes & Development Open Access Option.

Received May 20, 2015.
Accepted August 26, 2015.

This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.