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PMID: 23408909 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

COM-1 promotes homologous recombination during Caenorhabditis elegans meiosis by antagonizing Ku-mediated non-homologous end joining.

PLoS genetics ·Vol. 9 ·No. 2 ·2013-00-00 ·Pages e1003276

Lemmens BB, Johnson NM, Tijsterman M

Abstract

Successful completion of meiosis requires the induction and faithful repair of DNA double-strand breaks (DSBs). DSBs can be repaired via homologous recombination (HR) or non-homologous end joining (NHEJ), yet only repair via HR can generate the interhomolog crossovers (COs) needed for meiotic chromosome segregation. Here we identify COM-1, the homolog of CtIP/Sae2/Ctp1, as a crucial regulator of DSB repair pathway choice during Caenorhabditis elegans gametogenesis. COM-1-deficient germ cells repair meiotic DSBs via the error-prone pathway NHEJ, resulting in a lack of COs, extensive chromosomal aggregation, and near-complete embryonic lethality. In contrast to its yeast counterparts, COM-1 is not required for Spo11 removal and initiation of meiotic DSB repair, but instead promotes meiotic recombination by counteracting the NHEJ complex Ku. In fact, animals defective for both COM-1 and Ku are viable and proficient in CO formation. Further genetic dissection revealed that COM-1 acts parallel to the nuclease EXO-1 to promote interhomolog HR at early pachytene stage of meiotic prophase and thereby safeguards timely CO formation. Both of these nucleases, however, are dispensable for RAD-51 recruitment at late pachytene stage, when homolog-independent repair pathways predominate, suggesting further redundancy and/or temporal regulation of DNA end resection during meiotic prophase. Collectively, our results uncover the potentially lethal properties of NHEJ during meiosis and identify a critical role for COM-1 in NHEJ inhibition and CO assurance in germ cells.

MeSH Terms
Animals Antigens, Nuclear/genetics,metabolism Caenorhabditis elegans/genetics Caenorhabditis elegans Proteins/genetics,metabolism Cell Cycle Proteins/genetics Chromosome Segregation/genetics Crossing Over, Genetic DNA Breaks, Double-Stranded DNA End-Joining Repair/genetics DNA-Binding Proteins/genetics,metabolism Endodeoxyribonucleases/genetics,metabolism Germ Cells/metabolism Homologous Recombination/genetics Ku Autoantigen Meiosis/genetics Pachytene Stage/genetics
Chemicals
Antigens, Nuclear COM-1 protein, C elegans Caenorhabditis elegans Proteins Cell Cycle Proteins DNA-Binding Proteins Endodeoxyribonucleases meiotic recombination protein SPO11 Ku Autoantigen
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lemmens Bennie B L G
Department of Toxicogenetics, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
Johnson Nicholas M
Tijsterman Marcel
Conflict of Interest

The authors have declared that no competing interests exist.

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Article Info
Journal
PLoS genetics
Abbr.
PLoS Genet
ISSN
1553-7404
DOI
10.1371/journal.pgen.1003276
Published
2013-00-00
Epub
2013-00-07
Pages
e1003276
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC3567172
Subset
IM
Grants
European Research Council · 203379 · International
External Links
PubMed source DOI: 10.1371/journal.pgen.1003276 PMC Full Text View journal details
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