The Centriole Biogenesis Cycle: Temporal Mechanisms, Autonomy and Coupling to the Cell Cycle and Other Cellular...

Centrioles are cytoskeletal organelles whose duplication must occur with high temporal precision to ensure faithful cell division, ciliogenesis and tissue organization. Traditionally, the centriole biogenesis cycle has been viewed as a surrogate to the nuclear division cycle, particularly to oscillations in cyclin-dependent kinase (CDK) activity. In this chapter, we revisit classic experimental observations demonstrating that centriole duplication can proceed independently of DNA replication, transcription and CDK oscillations, thereby revealing an intrinsic autonomy in this cycle. We then discuss emerging molecular evidence identifying oscillatory dynamics of Polo-like kinase 4 (Plk4) as the core autonomous clock mechanism that initiates and times centriole biogenesis. Building on this framework, we examine mechanisms that entrain or couple the centriole cycle to the mitotic cycle, ciliogenesis and circadian rhythms, highlighting shared regulatory modules such as ubiquitin ligases and phosphatases. We explore the physiological importance of maintaining proper coupling between these cycles through examples of cancer pathologies and developmental defects that arise when centriole timing becomes uncoupled. Finally, we outline outstanding questions regarding the temporal machinery that governs the centriole biogenesis cycle, its evolution, and emerging therapeutic opportunities, positioning this cycle as a model system for understanding how autonomous cellular clocks integrate into broader temporal control programmes in biology.