Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

Affiliations

• 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.

PMID:  39236163  DOI: 10.1126/science.ado5178

Abstract

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 G1 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 G1. Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G1, 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类似蛋白着丝粒蛋白A（CENP-A）定义的染色体位点，在细胞分裂过程中通过促进动粒的组装与微管结合。着丝粒的维持需要在细胞周期的早期G1期由特定的蛋白质机制主动补充CENP-A，以弥补其在DNA复制后的稀释。周期蛋白依赖性激酶（CDKs）限制了CENP-A的沉积，使其每个细胞周期只能发生一次，并在早期G1期之外作为负调控因子。相反，Polo样激酶1（PLK1）在早期G1期促进CENP-A的沉积，但这一过程的分子细节尚不清楚。我们在此揭示了一个磷酸化网络，该网络将PLK1招募至沉积机制，并控制一个构象开关，许可CENP-A沉积反应。我们的研究结果阐明了PLK1如何促进着丝粒的表观遗传维持。