Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 2971K) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Google Scholar Articles by Mahadevaiah, S. K. Articles by Burgoyne, P. S. PubMed PubMed Citation Articles by Mahadevaiah, S. K. Articles by Burgoyne, P. S. Pubmed/NCBI databases Gene GEO Profiles HomoloGene Nucleotide Protein UniGene Related Collections Related In this Issue article Social Bookmarking                      What's this?

¹ Division of Stem Cell Biology and Developmental Genetics, Medical Research Council National Institute for Medical Research, London NW7 1AA, England, UK
² Institut National de la Santé et de la Recherche Medicale U741, Institut Jacques Monod, 75251 Paris, Cedex 05, France
³ Center for Reproductive Medicine, Academic Medical Center, University of Amsterdam, Amsterdam 1105 AZ, Netherlands
⁴ Department of Endocrinology and Metabolism, Faculty of Science, Utrecht University, Utrecht 3584 CH, Netherlands
⁵ Department of Genetics and Development, College of Physicians and Surgeons of Columbia University, New York, NY 10032

Correspondence to Paul S. Burgoyne: pburgoy{at}nimr.mrc.ac.uk

Chromosome synapsis during zygotene is a prerequisite for the timely homologous recombinational repair of meiotic DNA double-strand breaks (DSBs). Unrepaired DSBs are thought to trigger apoptosis during midpachytene of male meiosis if synapsis fails. An early pachytene response to asynapsis is meiotic silencing of unsynapsed chromatin (MSUC), which, in normal males, silences the X and Y chromosomes (meiotic sex chromosome inactivation [MSCI]). In this study, we show that MSUC occurs in Spo11-null mouse spermatocytes with extensive asynapsis but lacking meiotic DSBs. In contrast, three mutants (Dnmt3l, Msh5, and Dmc1) with high levels of asynapsis and numerous persistent unrepaired DSBs have a severely impaired MSUC response. We suggest that MSUC-related proteins, including the MSUC initiator BRCA1, are sequestered at unrepaired DSBs. All four mutants fail to silence the X and Y chromosomes (MSCI failure), which is sufficient to explain the midpachytene apoptosis. Apoptosis does not occur in mice with a single additional asynapsed chromosome with unrepaired meiotic DSBs and no disturbance of MSCI.

Abbreviations used in this paper: ATR, ataxia telangiectasia and Rad3 related; BAC, bacterial artificial chromosome; DSB, double-strand break; MSCI, meiotic sex chromosome inactivation; MSUC, meiotic silencing of unsynapsed chromatin; SCD, SQ/TQ cluster domain.

© 2008 Mahadevaiah et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related In this Issue article

BAD BREAKS DON'T DOOM MEIOTIC CELLS

Mitch Leslie
J. Cell Biol. 2008 182: 217. [Full Text] [PDF]

This article has been cited by other articles:

• Leslie, M. (2008). BAD BREAKS DON'T DOOM MEIOTIC CELLS. JCB 182: 217-217 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents