Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

• 成果类型: Article
• 署名作者: Conti, Duccio; Verza, Arianna Esposito; Pesenti, Marion E.; Cmentowski, Verena; Vetter, Ingrid R.; Pan, Dongqing; Musacchio, Andrea
• 署名单位: Max Planck Society; University of Duisburg Essen
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11183
• DOI: 10.1126/science.ado5178
• 发表日期: 2024-09-06
• 页码: 1091-1097
• 关键词: cenp-a chromatin; molecular-basis; histone h3; polo; RECRUITMENT; binding; deposition; mechanism; domain; phase

摘要

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(1) 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(1). Antithetically, Polo-like kinase 1 (PLK1) promotes CENP-A deposition in early G(1), 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.