CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis

Sihem Zitouni, Maria E. Francia, Filipe Leal, Susana Montenegro Gouveia, Catarina Nabais, Paulo Duarte, Samuel Gilberto, Daniela Brito, Tyler Moyer, Steffi Kandels-Lewis, Midori Ohta, Daiju Kitagawa, Andrew J. Holland, Eric Karsenti, Thierry Lorca, Mariana Lince-Faria, Mónica Bettencourt-Dias

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

Centrioles are essential for the assembly of both centrosomes and cilia. Centriole biogenesis occurs once and only once per cell cycle and is temporally coordinated with cell-cycle progression, ensuring the formation of the right number of centrioles at the right time. The formation of new daughter centrioles is guided by a pre-existing, mother centriole. The proximity between mother and daughter centrioles was proposed to restrict new centriole formation until they separate beyond a critical distance. Paradoxically, mother and daughter centrioles overcome this distance in early mitosis, at a time when triggers for centriole biogenesis Polo-like kinase 4 (PLK4) and its substrate STIL are abundant. Here we show that in mitosis, the mitotic kinase CDK1-CyclinB binds STIL and prevents formation of the PLK4-STIL complex and STIL phosphorylation by PLK4, thus inhibiting untimely onset of centriole biogenesis. After CDK1-CyclinB inactivation upon mitotic exit, PLK4 can bind and phosphorylate STIL in G1, allowing pro-centriole assembly in the subsequent S phase. Our work shows that complementary mechanisms, such as mother-daughter centriole proximity and CDK1-CyclinB interaction with centriolar components, ensure that centriole biogenesis occurs once and only once per cell cycle, raising parallels to the cell-cycle regulation of DNA replication and centromere formation.

Original languageEnglish (US)
Pages (from-to)1127-1137
Number of pages11
JournalCurrent Biology
Volume26
Issue number9
DOIs
StatePublished - May 9 2016

Keywords

  • CDK
  • PLK4
  • STIL
  • centriole duplication
  • centrosome
  • licensing
  • mitosis

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

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