蛋白激酶 PLK1 在中心粒表观遗传维持中的作用

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

Science Pub Date : 2024-09-05 DOI:10.1126/science.ado5178

Duccio Conti, Arianna Esposito Verza, Marion E. Pesenti, Verena Cmentowski, Ingrid R. Vetter, Dongqing Pan, Andrea Musacchio

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引用次数: 0

摘要

中心粒是由组蛋白 H3 样蛋白中心粒蛋白 A（CENP-A）定义的染色体位点，它能在细胞分裂过程中促进动核组装以结合微管。中心粒的维持需要 CENP-A 在细胞周期的早期 G1 阶段由专用蛋白质机制积极补充，以弥补其在 DNA 复制后的稀释。依赖细胞周期蛋白的激酶（CDKs）将 CENP-A 的沉积限制在每个细胞周期一次，并在 G1 早期之外发挥负调控作用。相反，Polo-like 激酶 1（PLK1）会促进 CENP-A 在 G1 早期的沉积，但这一过程的分子细节仍不清楚。我们在此揭示了一个磷酸化网络，该网络将 PLK1 招募到沉积机制，以控制许可 CENP-A 沉积反应所需的构象转换。我们的研究结果阐明了 PLK1 如何对中心粒的表观遗传维持做出贡献。

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Role of protein kinase PLK1 in the epigenetic maintenance of centromeres

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.

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来源期刊

Science 综合性期刊-综合性期刊

CiteScore

61.10

自引率

0.90%

发文量

审稿时长

2.1 months

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