Procentriole microtubules as drivers of centriole reduplication

ABSTRACT Centriole reduplication leads to the formation of supernumerary centrosomes, which promote cellular transformation, invasion and are a hallmark of tumors. A close association between a mother centriole and a procentriole (engagement), established during centriole duplication, intrinsically blocks reduplication. Premature loss of centriole association predisposes centrioles for reduplication and occurs during various types of cell cycle arrests in the presence of high Polo-like kinase 1 activity. Here we use nano-scale imaging and biochemistry to reveal the processes leading to the loss of centriole association and reduplication. We discover that centriole reduplication is driven by events occurring on procentriole microtubule walls. These events are mechanistically different from mitotic centriole separation driven by Pericentrin and Separase but are similar to the physiological process of centriole distancing occurring in unperturbed cycling G2 cells. We propose a concept in which centriole reduplication is a consequence of hijacked and amplified centriole maturation process. Highlights Separase-mediated Pericentrin reorganization is not required for centriole distancing and reduplication in interphase. Expression of active Plk1 in S phase leads to centrosomal ultrastructural changes resembling G2 phase. Procentrioles without microtubule walls cannot disengage. Centriole distancing is intrinsically regulated by the events occurring on procentriole microtubules.