Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1

Katrin Daniel, Julian Lange, Khaled Hached, Jun Fu, Konstantinos Anastassiadis, Ignasi Roig, Howard J. Cooke, A. Francis Stewart, Katja Wassmann, Maria Jasin, Scott Keeney, Attila Tóth*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

128 Citations (Scopus)

Abstract

Meiotic crossover formation between homologous chromosomes (homologues) entails DNA double-strand break (DSB) formation, homology search using DSB ends, and synaptonemal-complex formation coupled with DSB repair. Meiotic progression must be prevented until DSB repair and homologue alignment are completed, to avoid the formation of aneuploid gametes. Here we show that mouse HORMAD1 ensures that sufficient numbers of processed DSBs are available for successful homology search. HORMAD1 is needed for normal synaptonemal-complex formation and for the efficient recruitment of ATR checkpoint kinase activity to unsynapsed chromatin. The latter phenomenon was proposed to be important in meiotic prophase checkpoints in both sexes. Consistent with this hypothesis, HORMAD1 is essential for the elimination of synaptonemal-complex-defective oocytes. Synaptonemal-complex formation results in HORMAD1 depletion from chromosome axes. Thus, we propose that the synaptonemal complex and HORMAD1 are key components of a negative feedback loop that coordinates meiotic progression with homologue alignment: HORMAD1 promotes homologue alignment and synaptonemal-complex formation, and synaptonemal complexes downregulate HORMAD1 function, thereby permitting progression past meiotic prophase checkpoints.

Original languageEnglish
Pages (from-to)599-610
Number of pages12
JournalNature Cell Biology
Volume13
Issue number5
DOIs
Publication statusPublished - May 2011

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