PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance

IF 44.7 1区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES Science Pub Date : 2024-09-05 DOI:10.1126/science.ado8270

Pragya Parashara, Bethan Medina-Pritchard, Maria Alba Abad, Paula Sotelo-Parrilla, Reshma Thamkachy, David Grundei, Juan Zou, Christos Spanos, Chandni Natalia Kumar, Claire Basquin, Vimal Das, Zhaoyue Yan, Asma Abdullah Al-Murtadha, David A. Kelly, Toni McHugh, Axel Imhof, Juri Rappsilber, A. Arockia Jeyaprakash

{"title":"PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance","authors":"Pragya Parashara, Bethan Medina-Pritchard, Maria Alba Abad, Paula Sotelo-Parrilla, Reshma Thamkachy, David Grundei, Juan Zou, Christos Spanos, Chandni Natalia Kumar, Claire Basquin, Vimal Das, Zhaoyue Yan, Asma Abdullah Al-Murtadha, David A. Kelly, Toni McHugh, Axel Imhof, Juri Rappsilber, A. Arockia Jeyaprakash","doi":"10.1126/science.ado8270","DOIUrl":null,"url":null,"abstract":"<div >Accurate chromosome segregation requires the attachment of microtubules to centromeres, epigenetically defined by the enrichment of CENP-A nucleosomes. During DNA replication, CENP-A nucleosomes undergo dilution. To preserve centromere identity, correct amounts of CENP-A must be restored in a cell cycle–controlled manner orchestrated by the Mis18 complex (Mis18α-Mis18β-Mis18BP1). We demonstrate here that PLK1 interacts with the Mis18 complex by recognizing self-primed phosphorylations of Mis18α (Ser<sup>54</sup>) and Mis18BP1 (Thr<sup>78</sup> and Ser<sup>93</sup>) through its Polo-box domain. Disrupting these phosphorylations perturbed both centromere recruitment of the CENP-A chaperone HJURP and new CENP-A loading. Biochemical and functional analyses showed that phosphorylation of Mis18α and PLK1 binding were required to activate Mis18α-Mis18β and promote Mis18 complex-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.</div>","PeriodicalId":21678,"journal":{"name":"Science","volume":null,"pages":null},"PeriodicalIF":44.7000,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science","FirstCategoryId":"103","ListUrlMain":"https://www.science.org/doi/10.1126/science.ado8270","RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Accurate chromosome segregation requires the attachment of microtubules to centromeres, epigenetically defined by the enrichment of CENP-A nucleosomes. During DNA replication, CENP-A nucleosomes undergo dilution. To preserve centromere identity, correct amounts of CENP-A must be restored in a cell cycle–controlled manner orchestrated by the Mis18 complex (Mis18α-Mis18β-Mis18BP1). We demonstrate here that PLK1 interacts with the Mis18 complex by recognizing self-primed phosphorylations of Mis18α (Ser⁵⁴) and Mis18BP1 (Thr⁷⁸ and Ser⁹³) through its Polo-box domain. Disrupting these phosphorylations perturbed both centromere recruitment of the CENP-A chaperone HJURP and new CENP-A loading. Biochemical and functional analyses showed that phosphorylation of Mis18α and PLK1 binding were required to activate Mis18α-Mis18β and promote Mis18 complex-HJURP interaction. Thus, our study reveals key molecular events underpinning the licensing role of PLK1 in ensuring accurate centromere inheritance.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

PLK1 介导的磷酸化级联激活 Mis18 复合物，确保中心粒遗传。

染色体的准确分离需要微管附着在中心粒上，而中心粒是由 CENP-A 核小体的富集所决定的。在DNA复制过程中，CENP-A核小体会发生稀释。为了保持中心粒的特性，必须在 Mis18 复合物（Mis18α-Mis18β-Mis18BP1）的协调下以细胞周期控制的方式恢复 CENP-A 的正确数量。我们在此证明，PLK1通过其Polo-box结构域识别Mis18α（Ser54）和Mis18BP1（Thr78和Ser93）的自发磷酸化，从而与Mis18复合体相互作用。破坏这些磷酸化会扰乱 CENP-A 合子 HJURP 的中心粒招募和新的 CENP-A 负载。生化和功能分析显示，Mis18α的磷酸化和PLK1的结合是激活Mis18α-Mis18β和促进Mis18复合物-HJURP相互作用的必要条件。因此，我们的研究揭示了 PLK1 在确保准确的中心粒遗传中发挥许可作用的关键分子事件。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

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

期刊介绍： Science is a leading outlet for scientific news, commentary, and cutting-edge research. Through its print and online incarnations, Science reaches an estimated worldwide readership of more than one million. Science’s authorship is global too, and its articles consistently rank among the world's most cited research. Science serves as a forum for discussion of important issues related to the advancement of science by publishing material on which a consensus has been reached as well as including the presentation of minority or conflicting points of view. Accordingly, all articles published in Science—including editorials, news and comment, and book reviews—are signed and reflect the individual views of the authors and not official points of view adopted by AAAS or the institutions with which the authors are affiliated. Science seeks to publish those papers that are most influential in their fields or across fields and that will significantly advance scientific understanding. Selected papers should present novel and broadly important data, syntheses, or concepts. They should merit recognition by the wider scientific community and general public provided by publication in Science, beyond that provided by specialty journals. Science welcomes submissions from all fields of science and from any source. The editors are committed to the prompt evaluation and publication of submitted papers while upholding high standards that support reproducibility of published research. Science is published weekly; selected papers are published online ahead of print.