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蛋白激酶 PLK1 在着丝粒的表观遗传维持中的作用。

Role of protein kinase PLK1 in the epigenetic maintenance of centromeres.

机构信息

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.

出版信息

Science. 2024 Sep 6;385(6713):1091-1097. doi: 10.1126/science.ado5178. Epub 2024 Sep 5.

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 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.

摘要

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。

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