CDC6 controls dynamics of the first embryonic M-phase entry and progression via CDK1 inhibition

Mohammed El Dika, Katarzyna Laskowska-Kaszub, Magdalena Koryto, Damian Dudka, Claude Prigent, Jean Pierre Tassan, Malgorzata Kloc, Zbigniew Polanski, Ewa Borsuk, Jacek Z. Kubiak

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

CDC6 is essential for S-phase to initiate DNA replication. It also regulates M-phase exit by inhibiting the activity of the major M-phase protein kinase CDK1. Here we show that addition of recombinant CDC6 to Xenopus embryo cycling extract delays the M-phase entry and inhibits CDK1 during the whole M-phase. Down regulation of endogenous CDC6 accelerates the M-phase entry, abolishes the initial slow and progressive phase of histone H1 kinase activation and increases the level of CDK1 activity during the M-phase. All these effects are fully rescued by the addition of recombinant CDC6 to the extracts. Diminution of CDC6 level in mouse zygotes by two different methods results in accelerated entry into the first cell division showing physiological relevance of CDC6 in intact cells. Thus, CDC6 behaves as CDK1 inhibitor regulating not only the M-phase exit, but also the M-phase entry and progression via limiting the level of CDK1 activity. We propose a novel mechanism of M-phase entry controlled by CDC6 and counterbalancing cyclin B-mediated CDK1 activation. Thus, CDK1 activation proceeds with concomitant inhibition by CDC6, which tunes the timing of the M-phase entry during the embryonic cell cycle.

Original languageEnglish (US)
Pages (from-to)67-80
Number of pages14
JournalDevelopmental Biology
Volume396
Issue number1
DOIs
StatePublished - Dec 1 2014

Keywords

  • CDC6
  • CDK1
  • Cell-free extract
  • Embryo
  • M-phase entry
  • Mouse zygote
  • NCTD
  • Xenopus laevis

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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