Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis

Bilge Argunhan, Wing Kit Leung, Negar Afshar, Yaroslav Terentyev, Vijayalakshmi V. Subramanian, Yasuto Murayama, Andreas Hochwagen, Hiroshi Iwasaki, Tomomi Tsubouchi, Hideo Tsubouchi

Research output: Contribution to journalArticle

Abstract

The synaptonemal complex (SC) is a proteinaceous macromolecular assembly that forms during meiotic prophase I and mediates adhesion of paired homologous chromosomes along their entire lengths. Although prompt disassembly of the SC during exit from prophase I is a landmark event of meiosis, the underlying mechanism regulating SC destruction has remained elusive. Here, we show that DDK (Dbf4-dependent Cdc7 kinase) is central to SC destruction. Upon exit from prophase I, Dbf4, the regulatory subunit of DDK, directly associates with and is phosphorylated by the Polo-like kinase Cdc5. In parallel, upregulated CDK1 activity also targets Dbf4. An enhanced Dbf4-Cdc5 interaction pronounced phosphorylation of Dbf4 and accelerated SC destruction, while reduced/abolished Dbf4 phosphorylation hampered destruction of SC proteins. SC destruction relieved meiotic inhibition of the ubiquitous recombinase Rad51, suggesting that the mitotic recombination machinery is reactivated following prophase I exit to repair any persisting meiotic DNA double-strand breaks. Taken together, we propose that the concerted action of DDK, Polo-like kinase, and CDK1 promotes efficient SC destruction at the end of prophase I to ensure faithful inheritance of the genome.

Original languageEnglish (US)
Pages (from-to)2488-2509
Number of pages22
JournalEMBO Journal
Volume36
Issue number17
DOIs
StatePublished - Sep 1 2017

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Keywords

  • Dbf4-dependent Cdc7 kinase
  • Polo-like kinase
  • homologous recombination
  • meiosis
  • synaptonemal complex

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Argunhan, B., Leung, W. K., Afshar, N., Terentyev, Y., Subramanian, V. V., Murayama, Y., Hochwagen, A., Iwasaki, H., Tsubouchi, T., & Tsubouchi, H. (2017). Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis. EMBO Journal, 36(17), 2488-2509. https://doi.org/10.15252/embj.201695895