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PMID: 18787696 Published · epublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

MUS81 generates a subset of MLH1-MLH3-independent crossovers in mammalian meiosis.

PLoS genetics ·Vol. 4 ·No. 9 ·2008-09-12 ·Pages e1000186

Holloway JK, Booth J, Edelmann W, McGowan CH, Cohen PE

Abstract

Two eukaryotic pathways for processing double-strand breaks (DSBs) as crossovers have been described, one dependent on the MutL homologs Mlh1 and Mlh3, and the other on the structure-specific endonuclease Mus81. Mammalian MUS81 has been implicated in maintenance of genomic stability in somatic cells; however, little is known about its role during meiosis. Mus81-deficient mice were originally reported as being viable and fertile, with normal meiotic progression; however, a more detailed examination of meiotic progression in Mus81-null animals and WT controls reveals significant meiotic defects in the mutants. These include smaller testis size, a depletion of mature epididymal sperm, significantly upregulated accumulation of MLH1 on chromosomes from pachytene meiocytes in an interference-independent fashion, and a subset of meiotic DSBs that fail to be repaired. Interestingly, chiasmata numbers in spermatocytes from Mus81-/- animals are normal, suggesting additional integrated mechanisms controlling the two distinct crossover pathways. This study is the first in-depth analysis of meiotic progression in Mus81-nullizygous mice, and our results implicate the MUS81 pathway as a regulator of crossover frequency and placement in mammals.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Animals Carrier Proteins/genetics,metabolism Crossing Over, Genetic DNA Breaks, Double-Stranded DNA-Binding Proteins/genetics,metabolism Endonucleases/genetics,metabolism Female Fluorescent Antibody Technique Homozygote Male Meiosis/genetics Mice Mice, Knockout MutL Protein Homolog 1 MutL Proteins Mutation Nuclear Proteins/genetics,metabolism Oocytes/cytology,metabolism Sperm Count Testis/cytology,metabolism
Chemicals
Adaptor Proteins, Signal Transducing Carrier Proteins DNA-Binding Proteins Mlh1 protein, mouse Mlh3 protein, mouse Nuclear Proteins Endonucleases Mus81 protein, mouse MutL Protein Homolog 1 MutL Proteins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Holloway J Kim
Department of Biomedical Sciences, Cornell University, Ithaca, New York, United States of America.
Booth James
Edelmann Winfried
McGowan Clare H
Cohen Paula E
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.1000186
Published
2008-09-12
Epub
2008-00-12
Pages
e1000186
Language
English
Region
United States
NLM ID
101239074
PMCID
PMC2525838
Subset
IM
Grants
NICHD NIH HHS · R01 HD041012 · United States
NICHD NIH HHS · R56 HD041012 · United States
NICHD NIH HHS · HD041012 · United States
External Links
PubMed source DOI: 10.1371/journal.pgen.1000186 PMC Full Text View journal details
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