Loss of HR6B Ubiquitin-Conjugating Activity Results in Damaged Synaptonemal Complex Structure and Increased Crossing-Over Frequency during the Male Meiotic Prophase
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Published:2003-02-15
Issue:4
Volume:23
Page:1151-1162
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ISSN:0270-7306
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Container-title:Molecular and Cellular Biology
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language:en
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Short-container-title:Mol Cell Biol
Author:
Baarends Willy M.1, Wassenaar Evelyne1, Hoogerbrugge Jos W.1, van Cappellen Gert1, Roest Henk P.2, Vreeburg Jan1, Ooms Marja1, Hoeijmakers Jan H. J.2, Grootegoed J. Anton1
Affiliation:
1. Department of Reproduction and Development 2. Department of Cell Biology and Genetics, Erasmus University Rotterdam, 3000 DR Rotterdam, The Netherlands
Abstract
ABSTRACT
The ubiquitin-conjugating enzymes HR6A and HR6B are the two mammalian homologs of
Saccharomyces cerevisiae
RAD6. In yeast, RAD6 plays an important role in postreplication DNA repair and in sporulation.
HR6B
knockout mice are viable, but spermatogenesis is markedly affected during postmeiotic steps, leading to male infertility. In the present study, increased apoptosis of
HR6B
knockout primary spermatocytes was detected during the first wave of spermatogenesis, indicating that HR6B performs a primary role during the meiotic prophase. Detailed analysis of
HR6B
knockout pachytene nuclei showed major changes in the synaptonemal complexes. These complexes were found to be longer. In addition, we often found depletion of synaptonemal complex proteins from near telomeric regions in the
HR6B
knockout pachytene nuclei. Finally, we detected an increased number of foci containing the mismatch DNA repair protein MLH1 in these nuclei, reflecting a remarkable and consistent increase (20 to 25%) in crossing-over frequency. The present findings reveal a specific requirement for the ubiquitin-conjugating activity of HR6B in relation to dynamic aspects of the synaptonemal complex and meiotic recombination in spermatocytes.
Publisher
American Society for Microbiology
Subject
Cell Biology,Molecular Biology
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