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Curr Biol. 2016 May 9;26(9):1127-37. doi: 10.1016/j.cub.2016.03.055. Epub 2016 Apr 21.

CDK1 Prevents Unscheduled PLK4-STIL Complex Assembly in Centriole Biogenesis.

Author information

1
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: zsihem@igc.gulbenkian.pt.
2
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: mfrancia@igc.gulbenkian.pt.
3
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal.
4
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
5
Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany; Structural and Computational Biology, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany.
6
Center for Frontier Research, National Institute of Genetics, Yata 1111, Mishima, Shizuoka 411-8540, Japan.
7
Directors' Research, European Molecular Biology Laboratory, Meyerhofstrasse 1, Heidelberg 69117, Germany; Ecole Normale Supérieure, Institut de Biologie de l'ENS (IBENS), Inserm U1024, and CNRS UMR 8197, 46 Rue d'Ulm, Paris 75005, France.
8
Centre de Recherche de Biochimie Macromoléculaire, CNRS UMR 5237, 1919 Route de Mende, Montpellier 34293, France.
9
Instituto Gulbenkian de Ciência, Rua da Quinta Grande 6, Oeiras 2780-156, Portugal. Electronic address: mdias@igc.gulbenkian.pt.

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.

KEYWORDS:

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

PMID:
27112295
PMCID:
PMC4867225
DOI:
10.1016/j.cub.2016.03.055
[Indexed for MEDLINE]
Free PMC Article

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