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PMID: 20661436 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

Structural maintenance of chromosomes (SMC) proteins promote homolog-independent recombination repair in meiosis crucial for germ cell genomic stability.

PLoS genetics ·Vol. 6 ·No. 7 ·2010-07-22 ·Pages e1001028

Bickel JS, Chen L, Hayward J, Yeap SL, Alkers AE, Chan RC

Abstract

In meiosis, programmed DNA breaks repaired by homologous recombination (HR) can be processed into inter-homolog crossovers that promote the accurate segregation of chromosomes. In general, more programmed DNA double-strand breaks (DSBs) are formed than the number of inter-homolog crossovers, and the excess DSBs must be repaired to maintain genomic stability. Sister-chromatid (inter-sister) recombination is postulated to be important for the completion of meiotic DSB repair. However, this hypothesis is difficult to test because of limited experimental means to disrupt inter-sister and not inter-homolog HR in meiosis. We find that the conserved Structural Maintenance of Chromosomes (SMC) 5 and 6 proteins in Caenorhabditis elegans are required for the successful completion of meiotic homologous recombination repair, yet they appeared to be dispensable for accurate chromosome segregation in meiosis. Mutations in the smc-5 and smc-6 genes induced chromosome fragments and dismorphology. Chromosome fragments associated with HR defects have only been reported in mutants, which have disrupted inter-homolog crossover. Surprisingly, the smc-5 and smc-6 mutations did not disrupt the formation of chiasmata, the cytologically visible linkages between homologous chromosomes formed from meiotic inter-homolog crossovers. The mutant fragmentation defect appeared to be preferentially enhanced by the disruptions of inter-homolog recombination but not by the disruptions of inter-sister recombination. Based on these findings, we propose that the C. elegans SMC-5/6 proteins are required in meiosis for the processing of homolog-independent, presumably sister-chromatid-mediated, recombination repair. Together, these results demonstrate that the successful completion of homolog-independent recombination is crucial for germ cell genomic stability.

MeSH Terms
Caenorhabditis elegans Proteins/genetics,physiology Cell Cycle Proteins/genetics,physiology Chromosomal Proteins, Non-Histone/genetics,physiology Chromosomes DNA Breaks, Double-Stranded DNA Repair Genomic Instability Germ Cells/cytology Meiosis Mutation Recombination, Genetic
Chemicals
Caenorhabditis elegans Proteins Cell Cycle Proteins Chromosomal Proteins, Non-Histone
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Bickel Jeremy S
Department of Human Genetics, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.
Chen Liting
Hayward Jin
Yeap Szu Ling
Alkers Ashley E
Chan Raymond C
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.1001028
Published
2010-07-22
Epub
2010-00-22
Pages
e1001028
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2908675
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pgen.1001028 PMC Full Text View journal details
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