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PMID: 16055729 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Surveillance of different recombination defects in mouse spermatocytes yields distinct responses despite elimination at an identical developmental stage.

Molecular and cellular biology ·Vol. 25 ·No. 16 ·2005-08-00 ·Pages 7203-15

Barchi M, Mahadevaiah S, Di Giacomo M, Baudat F, de Rooij DG, Burgoyne PS, Jasin M, Keeney S

Abstract

Fundamentally different recombination defects cause apoptosis of mouse spermatocytes at the same stage in development, stage IV of the seminiferous epithelium cycle, equivalent to mid-pachynema in normal males. To understand the cellular response(s) that triggers apoptosis, we examined markers of spermatocyte development in mice with different recombination defects. In Spo11(-)(/)(-) mutants, which lack the double-strand breaks (DSBs) that initiate recombination, spermatocytes express markers of early to mid-pachynema, forming chromatin domains that contain sex body-associated proteins but that rarely encompass the sex chromosomes. Dmc1(-)(/)(-) spermatocytes, impaired in DSB repair, appear to arrest at or about late zygonema. Epistasis analysis reveals that this earlier arrest is a response to unrepaired DSBs, and cytological analysis implicates the BRCT-containing checkpoint protein TOPBP1. Atm(-)(/)(-) spermatocytes show similarities to Dmc1(-)(/)(-) spermatocytes, suggesting that ATM promotes meiotic DSB repair. Msh5(-)(/)(-) mutants display a set of characteristics distinct from these other mutants. Thus, despite equivalent stages of spermatocyte elimination, different recombination-defective mutants manifest distinct responses, providing insight into surveillance mechanisms in male meiosis.

MeSH Terms
Animals Apoptosis Chromatin/metabolism DNA Repair Epistasis, Genetic Fluorescent Antibody Technique, Indirect Gene Expression Regulation, Developmental Male Meiosis Mice Mice, Inbred C57BL Mice, Transgenic Microscopy, Fluorescence Models, Genetic Mutation Recombination, Genetic Spermatocytes/cytology,metabolism Testis/metabolism Time Factors
Chemicals
Chromatin
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Barchi Marco
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
Mahadevaiah Shantha
Di Giacomo Monica
Baudat Frédéric
de Rooij Dirk G
Burgoyne Paul S
Jasin Maria
Keeney Scott
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.25.16.7203-7215.2005
Published
2005-08-00
Pages
7203-15
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC1190256
Subset
IM
Grants
Medical Research Council · MC_U117532009 · United Kingdom
NICHD NIH HHS · R01 HD040916 · United States
NICHD NIH HHS · HD40916 · United States
External Links
PubMed source DOI: 10.1128/MCB.25.16.7203-7215.2005 PMC Full Text View journal details
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