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Molecular and Cellular Biology, August 2005, p. 7203-7215, Vol. 25, No. 16
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.16.7203-7215.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Surveillance of Different Recombination Defects in Mouse Spermatocytes Yields Distinct Responses despite Elimination at an Identical Developmental Stage

Marco Barchi,¹ Shantha Mahadevaiah,² Monica Di Giacomo,¹ Frédéric Baudat,^1, Dirk G. de Rooij,³ Paul S. Burgoyne,² Maria Jasin,^1* and Scott Keeney^1*

Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,¹ Division of Stem Cell Research and Developmental Genetics, MRC National Institute for Medical Research, London NW7 1AA, United Kingdom,² Department of Endocrinology, Faculty of Biology, Utrecht University, and Department of Cell Biology, UMCU, Utrecht, The Netherlands³

Received 28 April 2005/ Returned for modification 24 May 2005/ Accepted 27 May 2005

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.

Present address: Institut de Génétique Humaine, Montpellier, France.

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