Cep63 and cep152 cooperate to ensure centriole duplication.
Centrosomes consist of two centrioles embedded in pericentriolar material and function as the main microtubule organising centres in dividing animal cells. They ensure proper formation and orientation of the mitotic spindle and are therefore essential for the maintenance of genome stability. Centrosome function is crucial during embryonic development, highlighted by the discovery of mutations in genes encoding centrosome or spindle pole proteins that cause autosomal recessive primary microcephaly, including Cep63 and Cep152. In this study we show that Cep63 functions to ensure that centriole duplication occurs reliably in dividing mammalian cells. We show that the interaction between Cep63 and Cep152 can occur independently of centrosome localisation and that the two proteins are dependent on one another for centrosomal localisation. Further, both mouse and human Cep63 and Cep152 cooperate to ensure efficient centriole duplication by promoting the accumulation of essential centriole duplication factors upstream of SAS-6 recruitment and procentriole formation. These observations describe the requirement for Cep63 in maintaining centriole number in dividing mammalian cells and further establish the order of events in centriole formation.
Cancer Research UK London Research Institute, Clare Hall Laboratories, South Mimms, United Kingdom.
Nicola J
NJ
Brown
Marko
M
Marjanović
Jens
J
Lüders
Travis H
TH
Stracker
Vincenzo
V
Costanzo
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002502:Centrioles / Q000235:genetics / Q000378:metabolism*; D018385:Centrosome / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D006801:Humans; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
C551028:CEP152 protein, human; C508298:CEP63 protein, human; D018797:Cell Cycle Proteins; C526596:Cep192 protein, human; D002868:Chromosomal Proteins, Non-Histone; D009363:Neoplasm Proteins; C497202:SASS6 protein, human