SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells

Author:  ["Sebastian Leidel","Marie Delattre","Lorenzo Cerutti","Karine Baumer","Pierre Gönczy"]

Publication:  Nature Cell Biology

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Tags:  general   CellBiology   CancerResearch   DevelopmentalBiology   StemCells   Biological

Abstract

The mechanisms that ensure centrosome duplication are poorly understood. In Caenorhabditis elegans, ZYG-1, SAS-4, SAS-5 and SPD-2 are required for centriole formation. However, it is unclear whether these proteins have functional homologues in other organisms. Here, we identify SAS-6 as a component that is required for daughter centriole formation in C. elegans. SAS-6 is a coiled-coil protein that is recruited to centrioles at the onset of the centrosome duplication cycle. Our analysis indicates that SAS-6 and SAS-5 associate and that this interaction, as well as ZYG-1 function, is required for SAS-6 centriolar recruitment. SAS-6 is the founding member of an evolutionarily conserved protein family that contains the novel PISA motif. We investigated the function of the human homologue of SAS-6. GFP–HsSAS-6 localizes to centrosomes and its overexpression results in excess foci-bearing centriolar markers. Furthermore, siRNA-mediated inactivation of HsSAS-6 in U2OS cells abrogates centrosome overduplication following aphidicolin treatment and interferes with the normal centrosome duplication cycle. Therefore, HsSAS-6 is also required for centrosome duplication, indicating that the function of SAS-6-related proteins has been widely conserved during evolution.

Cite this article

Leidel, S., Delattre, M., Cerutti, L. et al. SAS-6 defines a protein family required for centrosome duplication in C. elegans and in human cells. Nat Cell Biol 7, 115–125 (2005). https://doi.org/10.1038/ncb1220

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