Developmental Cell 16, 649–660, May 19, 2009

Cep76, a Centrosomal Protein that Specifically Restrains Centriole Reduplication
William Y. Tsang, Alexander Spektor,Sangeetha Vijayakumar, Bigyan R. Bista, Ji Li, Irma Sánchez, Stefan Duensing, and Brian D. Dynlacht

Cep76 helps limit centriole duplication to once per cell cycle

Centrosomes duplicate just once per cell cycle, and yet the mechanisms that govern this process are largely unknown. In an effort to dissect the controls regulating the duplication of centrosomes, we have attempted to identify proteins associated with the centriolar protein CP110. Our laboratory first identified CP110 as a centriolar CDK2 substrate, and subsequent work have established this gene as an important player in centrosome function (Chen et al., 2002). Ablation of CP110 CDK2 phospho-acceptor sites gives rise to unscheduled centrosome separation and polyploidy. Depletion of this protein prevents centrosome amplification during prolonged S phase arrest and leads to premature centrosome separation, and causes cytokinesis defects (Chen et al., 2002; Tsang et al., 2006). Ultrastructural studies show that CP110 plays an early role in centriole biogenesis, during which it associates with the distal tip of growing procentrioles. In this report, we begin the characterization of an interacting protein, Cep76. We show that Cep76 associates with CP110 and a second CP110-interacting protein, Cep97. Cep76 localizes to centrosomes and is expressed in a cell cycle-dependent manner, peaking in S and G2 phase cells. Interestingly, depletion of Cep76 drives the accumulation of centriolar intermediates in certain types of cancer cells. In contrast, enforced Cep76 expression specifically inhibits centriole amplification in cells undergoing multiple rounds of duplication without preventing the formation of extra procentrioles from a parental template. Furthermore, elevated levels of Cep76 do not affect normal centriole duplication. Thus, Cep76 helps limit duplication to once per cell cycle.