PLK1-mediated phosphorylation cascade activates Mis18 complex to ensure centromere inheritance
Open accessPublished version of a preprint
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 (Ser 54 ) and Mis18BP1 (Thr 78 and Ser 93 ) 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.
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References 62 · Cited by 36
- Authors
- Parashara, P., Medina-Pritchard, B., Abad, M. A., Sotelo-Parrilla, P., Thamkachy, R., Grundei, D., Zou, J., Spanos, C., Kumar, C. N., Basquin, C., Das, V., Yan, Z., Al-Murtadha, A. A., Kelly, D. A., McHugh, T., Imhof, A., Rappsilber, J., & Jeyaprakash, A. A.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Wellcome Centre for Cell Biology, University of Edinburgh, Edinburgh EH9 3BF, UK.
- Gene Center Munich, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
- Ludwig-Maximilians-Universität München (DE)
- Department of Structural Biology, Max Planck Institute of Biochemistry, D-82152 Martinsried, Germany.
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Parashara, Pragya
- Abad, Maria Alba
- Jeyaprakash, A. Arockia
- ORCID
- Venue
- Science
- Published
- 2024-09-06
- Volume
- 385
- Issue
- 6713
- Pages
- 1098-1104
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4402263012
- Cited by
- 36
- References
- 62
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 4
- FWCI
- 8.13
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Licence
- cc-by
- Locations
- Science (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (publishedVersion, cc-by)
- Funders
- Wellcome Trust (203149)
- Medical Research Council (MR/X001245/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Keywords
- PLK1, CENP-A, HJURP, phosphorylation cascade, polo-box domain, chromosome segregation, centromere identity, DNA replication
- MeSH terms
- Centromere Protein A, Polo-Like Kinase 1, Centromere, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, HeLa Cells, Humans, Phosphorylation, Proto-Oncogene Proteins, Protein Serine-Threonine Kinases, Cell Cycle Proteins, Chromosome Segregation, Adaptor Proteins, Signal Transducing
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