title: Overly long centrioles and defective cell division upon excess of the SAS-4-related protein CPAP.
abstract: The centrosome is the principal microtubule organizing center (MTOC) of animal cells. Accurate centrosome duplication is fundamental for genome integrity and entails the formation of one procentriole next to each existing centriole, once per cell cycle. The procentriole then elongates to eventually reach the same size as the centriole. The mechanisms that govern elongation of the centriolar cylinder and their potential relevance for cell division are not known. Here, we show that the SAS-4-related protein CPAP is required for centrosome duplication in cycling human cells. Furthermore, we demonstrate that CPAP overexpression results in the formation of abnormally long centrioles. This also promotes formation of more than one procentriole in the vicinity of such overly long centrioles, eventually resulting in the presence of supernumerary MTOCs. This in turn leads to multipolar spindle assembly and cytokinesis defects. Overall, our findings suggest that centriole length must be carefully regulated to restrict procentriole number and thus ensure accurate cell division.
authors.affiliation: Swiss Institute for Experimental Cancer Research (ISREC), School of Life Sciences, Swiss Federal Institute of Technology (EPFL), Lausanne, Switzerland.
authors.forename: Gregor
authors.initials: G
authors.lastname: Kohlmaier
authors.forename: Jadranka
authors.initials: J
authors.lastname: Loncarek
authors.forename: Xing
authors.initials: X
authors.lastname: Meng
authors.forename: Bruce F
authors.initials: BF
authors.lastname: McEwen
authors.forename: Mette M
authors.initials: MM
authors.lastname: Mogensen
authors.forename: Alexander
authors.initials: A
authors.lastname: Spektor
authors.forename: Brian D
authors.initials: BD
authors.lastname: Dynlacht
authors.forename: Alexey
authors.initials: A
authors.lastname: Khodjakov
authors.forename: Pierre
authors.initials: P
authors.lastname: Gönczy
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002455:Cell Division / Q000502:physiology*; D002460:Cell Line; D002502:Centrioles / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism / Q000648:ultrastructure
chemical_list: C414735:CENPJ protein, human; D008869:Microtubule-Associated Proteins; D011993:Recombinant Fusion Proteins