Autor(es):
Zitouni, Sihem ; Francia, Maria E. ; Leal, Filipe ; Montenegro Gouveia, Susana ; Nabais, Catarina ; Duarte, Paulo ; Gilberto, Samuel ; Brito, Daniela ; Moyer, Tyler ; Kandels-Lewis, Steffi ; Ohta, Midori ; Kitagawa, Daiju ; Holland, Andrew J. ; Karsenti, Eric ; Lorca, Thierry ; Lince-Faria, Mariana ; Bettencourt-Dias, Mónica
Data: 2016
Identificador Persistente: http://hdl.handle.net/10400.7/831
Origem: ARCA - Access to Research and Communication Annals
Assunto(s): PLK4; CDK; STIL; mitosis; centriole duplication; licensing; centrosome
Descrição
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.
