Regulated HsSAS-6 levels ensure formation of a single procentriole per centriole during the centrosome duplication cycle.
Centrosome duplication involves the formation of a single procentriole next to each centriole, once per cell cycle. The mechanisms governing procentriole formation and those restricting its occurrence to one event per centriole are poorly understood. Here, we show that HsSAS-6 is necessary for procentriole formation and that it localizes asymmetrically next to the centriole at the onset of procentriole formation. HsSAS-6 levels oscillate during the cell cycle, with the protein being degraded in mitosis and starting to accumulate again at the end of the following G1. Our findings indicate that APC(Cdh1) targets HsSAS-6 for degradation by the 26S proteasome. Importantly, we demonstrate that increased HsSAS-6 levels promote formation of more than one procentriole per centriole. Therefore, regulated HsSAS-6 levels normally ensure that each centriole seeds the formation of a single procentriole per cell cycle, thus playing a fundamental role in driving the centrosome duplication cycle and ensuring genome integrity.
Swiss Institute for Experimental Cancer Research, Swiss Federal Institute of Technology, School of Life Sciences, CH-1066 Lausanne, Switzerland.
Petr
P
Strnad
Sebastian
S
Leidel
Tatiana
T
Vinogradova
Ursula
U
Euteneuer
Alexey
A
Khodjakov
Pierre
P
Gönczy
D000705:Anaphase; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002502:Centrioles / Q000378:metabolism* / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D021381:Protein Transport
D018797:Cell Cycle Proteins; C497202:SASS6 protein, human; C490219:PLK4 protein, human; D017346:Protein Serine-Threonine Kinases; D046988:Proteasome Endopeptidase Complex; C061553:ATP dependent 26S protease