1. PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance.
- Author
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Parashara, Pragya, Medina-Pritchard, Bethan, Abad, Maria Alba, Sotelo-Parrilla, Paula, Thamkachy, Reshma, Grundei, David, Juan Zou, Spanos, Christos, Kumar, Chandni Natalia, Basquin, Claire, Das, Vimal, Zhaoyue Yan, Al-Murtadha, Asma Abdullah, Kelly, David A., McHugh, Toni, Imhof, Axel, Rappsilber, Juri, and Jeyaprakash, A. Arockia
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CENTROMERE , *PHOSPHORYLATION , *HEREDITY , *CHROMOSOME segregation , *DNA replication , *HEMODILUTION , *TUBULINS - 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. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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