Presentation/Session Information

Session Information

Session Title: Cell Division and Cell Death Session Type: Parallel
Session Location: Northwest Auditorium Session Time: Thu, Jun 25 8:30AM - 11:30AM

Presentation Information

Program Number: 58 Presentation Time: 10:54AM - 11:06AM

Presentation Content

The molecular identification of a gene which controls the distribution of meiotic recombination events in Caenorhabditis elegans.George Chung 1, Ann Rose 1, Mark Petalcorin 2, Nigel O'Neil 1, Jeffrey Chu 1, Julie Martin 2, Zebulin Kessler 3, Luis Sanchez-Pulido 4, Chris Ponting 4, Judith Yanowitz 3, Simon Boulton 2. 1)Department of Medical Genetics, University of British Columbia, Vancouver, BC; 2)DNA Damage Response Laboratory, London Research Institute, Clare Hall Laboratories, South Mimms, UK; 3)Magee-Womens Research Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA; 4)MRC Functional Genomics Unit, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK

The placement of meiotic crossover events is regulated such that crossover events are not distributed randomly along the chromosome. In Caenorhabditis elegans, meiotic crossover placement favours chromosome arms over chromosome centres, a bias abolished by mutations in the rec-1 gene. This mutant phenotype has precluded positional cloning efforts for 30 years. Here, we describe the identity of rec-1, which was uncovered by whole-genome sequencing and confirmed by new alleles engineered with MosSCI and CRISPR-Cas9. The rec-1 gene encodes a previously uncharacterized protein, which possesses putative phosphorylation motifs as well as weak homology to the meiotic protein HIM-5. We demonstrate that the REC-1 protein is a substrate for CDK phosphorylation in vitro and in C. elegans extracts. This phosphorylation was abolished in a REC-1(8A) mutant lacking the 8 CDK phosphorylation sites. Moreover, the rec-1(8A) and rec-1(8E) (phosphor-mimetic) mutant transgenes did not rescue the rec-1 defect. Given the homology shared between REC-1 and HIM-5, we also examined their genetic relationship. Strikingly, we found that in contrast to the single mutants, the rec-1; him-5 double mutant was defective for the formation of meiotic double-strand breaks (DSBs), which was rescued by artificially introducing DSBs using ionizing radiation. Thus, we establish that REC-1 plays an indispensable role in the distribution of meiotic crossovers, which is controlled by CDK phosphorylation. Furthermore, we uncover an unappreciated redundancy in the mechanisms required to generate meiotic DSBs involving REC-1 and HIM-5.




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