Once and only once: mechanisms of centriole duplication and their deregulation in disease

Key Points Centrosome duplication is tightly regulated to ensure that centrioles duplicate only once per cell cycle and that only one new centriole is produced per pre-existing centriole Phosphorylation events have an important role in controlling centriole number. Polo-like kinase 1 (PLK1) has a key function in cell cycle control of centriole duplication, whereas PLK4 takes centre stage in controlling centriole copy number Recent work has uncovered the existence of distinct signalling pathways that limit the proliferation of cells with an increase or decrease in centrosome number The presence of extra centrosomes can endow cells with oncogenic properties. However, overcoming the inhibitory effect of extra centrosomes on cell proliferation is necessary to allow cells with extra centrosomes to sustain the cell divisions required for tumour development Primary microcephaly may be caused by deregulation of centriole numbers and, potentially, by pathological activation of the mitotic surveillance pathway, and in consequence cell cycle arrest or apoptosis, in the developing brain Most eukaryotic cells contain a single centrosome with a pair of centrioles, which duplicate before mitosis. Defects in duplication lead to aberrant numbers of centrioles and centrosomes. Recent insights into mechanisms of centriole biogenesis and centriole number control are helping us to better understand the links between aberrant centrosome number and human disease. Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule-related processes, including motility, cell division and cell signalling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each pre-existing centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these processes contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit the proliferation of cells with numerical centriole aberrations. Owing to this progress, we now have a better understanding of the molecular mechanisms governing centriole biogenesis, opening up new po