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.
Highlights
DNA double-strand breaks (DSBs) are one of the most deleterious lesions to our genome yet are induced during meiosis to promote the exchange of genetic material between homologous chromosomes
A recessive mutation in the rec-1 gene randomizes the distribution of the meiotic recombination events while preserving crossover interference such that an increased crossover frequency in the autosomal centers is accompanied by a decreased crossover frequency in the autosomal arms (Rose and Baillie 1979; Zetka and Rose 1995)
Because of this altered recombination phenotype and the absence of any additional effects on development or fecundity (Rattray and Rose 1988), mapping of GENES & DEVELOPMENT 29:1969–1979 Published by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/15; www.genesdev.org rec-1 by conventional linkage analysis was not possible, and the identity of C. elegans rec-1 remained unknown for >30 years after the description of its mutant phenotype
Summary
DNA double-strand breaks (DSBs) are one of the most deleterious lesions to our genome yet are induced during meiosis to promote the exchange of genetic material between homologous chromosomes. Rec-1 was the first locus described in C. elegans to exert such genetic control of the meiotic crossover pattern without perturbing crossover interference Because of this altered recombination phenotype and the absence of any additional effects on development or fecundity (Rattray and Rose 1988), mapping of GENES & DEVELOPMENT 29:1969–1979 Published by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/15; www.genesdev.org rec-1 by conventional linkage analysis was not possible, and the identity of C. elegans rec-1 remained unknown for >30 years after the description of its mutant phenotype. Our data highlight an evolutionary and functional relationship between rec-1 and him-5 in the generation of meiotic DSBs and their distribution on meiotic chromosomes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
