Final Report Summary - CENDUP (Decoding the mechanisms of centrosome duplication)
The centriole is an evolutionary conserved organelle that is critical for the assembly of cilia and flagella, as well as that of centrosomes in animal cells. The centriole is characterized by a striking nine-fold radially symmetric arrangement of microtubules that assemble around a cartwheel structure. The mechanisms governing centriole formation remain incompletely understood and constitute a fundamental open question in cell and developmental biology. We have pursued an innovative multidisciplinary research program to gain novel insight into these mechanisms. Of particular importance, we have discovered that proteins of the SAS-6 family can assemble into ring-like structures with a nine-fold symmetry that resemble the cartwheel present at the onset of centriole formation. Moreover, we have conducted an siRNA-based functional genomic screen that enabled us to identify novel genes that regulate centriole number in human cells. Together, these and other findings have led to a better understanding of the mechanisms governing centriole formation.