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

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.