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)
JournalEMBO Journal
DOIs
StateAccepted/In press - 2017

Fingerprint

Synaptonemal Complex
Meiosis
Meiotic Prophase I
Cell Cycle
Phosphotransferases
Cells
Phosphorylation
Rad51 Recombinase
Chromosomes
Machinery
Repair
Adhesion
Genes
Double-Stranded DNA Breaks
Genetic Recombination
DNA
Genome
Proteins

Keywords

  • Dbf4-dependent Cdc7 kinase
  • Homologous recombination
  • Meiosis
  • Polo-like kinase
  • Synaptonemal complex

ASJC Scopus subject areas

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

Cite this

Argunhan, B., Leung, W. K., Afshar, N., Terentyev, Y., Subramanian, V. V., Murayama, Y., ... Tsubouchi, H. (Accepted/In press). Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis. EMBO Journal. https://doi.org/10.15252/embj.201695895

Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis. / Argunhan, Bilge; Leung, Wing Kit; Afshar, Negar; Terentyev, Yaroslav; Subramanian, Vijayalakshmi V.; Murayama, Yasuto; Hochwagen, Andreas; Iwasaki, Hiroshi; Tsubouchi, Tomomi; Tsubouchi, Hideo.

In: EMBO Journal, 2017.

Research output: Contribution to journalArticle

Argunhan, B, Leung, WK, Afshar, N, Terentyev, Y, Subramanian, VV, 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. https://doi.org/10.15252/embj.201695895
Argunhan, Bilge ; Leung, Wing Kit ; Afshar, Negar ; Terentyev, Yaroslav ; Subramanian, Vijayalakshmi V. ; Murayama, Yasuto ; Hochwagen, Andreas ; Iwasaki, Hiroshi ; Tsubouchi, Tomomi ; Tsubouchi, Hideo. / Fundamental cell cycle kinases collaborate to ensure timely destruction of the synaptonemal complex during meiosis. In: EMBO Journal. 2017.
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