Department of Mechanistic Cell Biology, Max Planck Institute of Molecular Physiology, 44227 Dortmund, Germany.
Centre for Medical Biotechnology, Faculty of Biology, University of Duisburg-Essen, 45141 Essen, Germany.
Science. 2024 Sep 6;385(6713):1091-1097. doi: 10.1126/science.ado5178. Epub 2024 Sep 5.
The centromere, a chromosome locus defined by the histone H3-like protein centromeric protein A (CENP-A), promotes assembly of the kinetochore to bind microtubules during cell division. Centromere maintenance requires CENP-A to be actively replenished by dedicated protein machinery in the early G phase of the cell cycle to compensate for its dilution after DNA replication. Cyclin-dependent kinases (CDKs) limit CENP-A deposition to once per cell cycle and function as negative regulators outside of early G. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G, but the molecular details of this process are still unknown. We reveal here a phosphorylation network that recruits PLK1 to the deposition machinery to control a conformational switch required for licensing the CENP-A deposition reaction. Our findings clarify how PLK1 contributes to the epigenetic maintenance of centromeres.
着丝粒是由组蛋白 H3 样蛋白着丝粒蛋白 A(CENP-A)定义的染色体位点,它在细胞分裂过程中促进动粒的组装以结合微管。着丝粒的维持需要在细胞周期的早期 G 期通过专门的蛋白质机制主动补充 CENP-A,以补偿 DNA 复制后其稀释。细胞周期蛋白依赖性激酶(CDK)限制 CENP-A 沉积在每个细胞周期中仅发生一次,并在早期 G 期之外作为负调节剂发挥作用。相反,Polo 样激酶 1(PLK1)在早期 G 期促进 CENP-A 的沉积,但该过程的分子细节仍不清楚。我们在这里揭示了一个磷酸化网络,该网络将 PLK1 募集到沉积机制中,以控制 CENP-A 沉积反应所需的构象开关。我们的研究结果阐明了 PLK1 如何有助于着丝粒的表观遗传维持。