Speculative model for a mechanism to limit centriole duplication to once per cell cycle by modulating the levels of Plk4 on centrioles through the activity of the SCF^Slimb ubiquitin ligase. (1) Plk4 levels on centrioles peak during mitosis but also appear asymmetrically positioned on centrioles in a subpopulation of interphase cells. At this time, Plk4 activity initiates the duplication process by ”priming” centrioles for the duplication event that occurs later in the cell cycle. This could be achieved by targeting or stabilizing a key centriolar subunit to the parent centriole that then lays the foundation to assemble a procentriole. During mitotic exit, centriole pairs separate (disengage), thereby releasing centriole singlets into the interphase cytoplasm (Callaini and Riparbelli, 1990). Although Slimb localizes to centrioles during all of the cell cycle phases that we examined, Plk4 is not phosphorylated on residues required for Slimb binding during mitosis and is thus stable. (2) As cells complete cytokinesis, centriole singlets shed their PCM and lack microtubule nucleating activity (Rogers et al., 2008). During interphase, Plk4 is phosphorylated and now recognized by SCF^Slimb, leading to its ubiquitination and degradation. Levels of centriole-associated Plk4 are low at this time. However, centrioles retain a critical modification (shown in purple) endowed upon them by Plk4 and are competent to duplicate. We note that Slimb and Plk4 levels on centrioles have not been determined during G1 phase. (3) Centrioles duplicate just before or during S phase with the appearance of a procentriole. Slimb on centrioles ensures that Plk4 levels remain low at this time and thus block centriole reduplication. (4) During G2, daughter centrioles elongate. Slimb at centrioles continues to prevent Plk4 accumulation.