Centriole structural integrity defects are a crucial feature of Hydrolethalus Syndrome.

Hydrolethalus Syndrome (HLS) is a lethal, autosomal recessive ciliopathy caused by the mutation of the conserved centriole protein HYLS1. However, how HYLS1 facilitates the centriole-based templating of cilia is poorly understood. Here, we show that mice harboring the HYLS1 disease mutation die shortly after birth and exhibit developmental defects that recapitulate several manifestations of the human disease.

Weakened APC/C activity at mitotic exit drives cancer vulnerability to KIF18A inhibition.

The efficacy of current antimitotic cancer drugs is limited by toxicity in highly proliferative healthy tissues. A cancer-specific dependency on the microtubule motor protein KIF18A therefore makes it an attractive therapeutic target. Not all cancers require KIF18A, however, and the determinants underlying this distinction remain unclear.

PLK1 promotes the mitotic surveillance pathway by controlling cytosolic 53BP1 availability.

53BP1 acts at the crossroads between DNA repair and p53-mediated stress response. With its interactors p53 and USP28, it is part of the mitotic surveillance (or mitotic stopwatch) pathway (MSP), a sensor that monitors the duration of cell division, promoting p53-dependent cell cycle arrest when a critical time threshold is surpassed. Here, we show that Polo-like kinase 1 (PLK1) activity is essential for the time-dependent release of 53BP1 from kinetochores.

PLK4 self-phosphorylation drives the selection of a single site for procentriole assembly.

Polo-like kinase 4 (PLK4) is a key regulator of centriole biogenesis, but how PLK4 selects a single site for procentriole assembly remains unclear. Using ultrastructure expansion microscopy, we show that PLK4 localizes to discrete sites along the wall of parent centrioles. While there is variation in the number of sites PLK4 occupies on the parent centriole, most PLK4 localize at a dominant site that directs procentriole assembly.

Keeping track of time: The fundamentals of cellular clocks.

Biological timekeeping enables the coordination and execution of complex cellular processes such as developmental programs, day/night organismal changes, intercellular signaling, and proliferative safeguards. While these systems are often considered separately owing to a wide variety of mechanisms, time frames, and outputs, all clocks are built by calibrating or delaying the rate of biochemical reactions and processes. In this review, we explore the common themes and core design principles of cellular clocks, giving special consideration to the challenges associated with building timers from biochemical components.