研究人员表示,着丝粒是由类组蛋白H3的着丝粒蛋白A(CENP-A)定义的染色体区域,它在细胞分裂期间通过促进动粒的组装来结合微管。着丝粒的维持需要在细胞周期早期G1期,由专门的蛋白质机制主动补充CENP-A,以弥补其在DNA复制后的稀释。
周期依赖性激酶(CDK)限制CENP-A的沉积每个细胞周期只发生一次,并在早期G1期之外充当负调控因子。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仍不清楚。
研究人员揭示了一个磷酸化网络,它将PLK1招募到沉积机制中,以控制一个构象转换,从而为CENP-A沉积反应提供许可。该研究阐明了PLK1如何促进着丝粒的表观遗传维持。
附:英文原文
Title: Role of protein kinase PLK1 in the epigenetic maintenance of centromeres
Author: Duccio Conti, Arianna Esposito Verza, Marion E. Pesenti, Verena Cmentowski, Ingrid R. Vetter, Dongqing Pan, Andrea Musacchio
Issue&Volume: 2024-09-06
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.
DOI: ado5178
Source: https://www.science.org/doi/10.1126/science.ado5178