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Molecular basis for Cdk1‐regulated timing of Mis18 complex assembly and CENP‐A deposition
Open accessAbstract
The centromere, a chromosomal locus that acts as a microtubule attachment site, is epigenetically specified by the enrichment of CENP-A nucleosomes. Centromere maintenance during the cell cycle requires HJURP-mediated CENP-A deposition, a process regulated by the Mis18 complex (Mis18α/Mis18β/Mis18BP1). Spatial and temporal regulation of Mis18 complex assembly is crucial for its centromere association and function. Here, we provide the molecular basis for the assembly and regulation of the Mis18 complex. We show that the N-terminal region of Mis18BP1 spanning amino acid residues 20-130 directly interacts with Mis18α/β to form the Mis18 complex. Within Mis18α/β, the Mis18α MeDiY domain can directly interact with Mis18BP1. Mis18α/β forms a hetero-hexamer with 4 Mis18α and 2 Mis18β. However, only two copies of Mis18BP1 interact with Mis18α/β to form a hetero-octameric assembly, highlighting the role of Mis18 oligomerization in limiting the number of Mis18BP1 within the Mis18 complex. Furthermore, we demonstrate the involvement of consensus Cdk1 phosphorylation sites on Mis18 complex assembly and thus provide a rationale for cell cycle-regulated timing of Mis18 assembly and CENP-A deposition.
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Micro3 showed similarities to HM_3, HM_4 but also expressed APOE, apoptosis associated genes XAF1, YWHAB, YWHAG, YWHAE, cell-cycle and cell division control genes CDK12, MIS18BP1, TAF1D, BOD1L1 and CCAR1.
“Micro3 showed similarities to HM_3, HM_4 phenotype but also expressed APOE, apoptosis associated genes XAF1, YWHAB, YWHAG, YWHAE encoding 14–3-3 protein subunits, cell-cycle and cell division control genes CDK12, MIS18BP1, TAF1D, BOD1L1 and CCAR1 [6, 30, 67].”
From Characterisation of premature cell senescence in Alzheimer's disease using single nuclear transcriptomics (2024) · cites this paper as [67]
The Introduction and Results and Discussion (page not specified in our copy) link MIS18BP1 to cell-cycle-regulated centromere maintenance and CENP-A deposition, supporting its characterization as related to cell division. They do not report a Micro3 phenotype, expression of these genes in Micro3, or the functions of the other listed genes. (LLM, conf=0.88)
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- Subramanian L, Medina‐Pritchard B, Barton R, Spiller F, Kulasegaran‐Shylini R, Radaviciute G, Allshire RC, Jeyaprakash AA (2016) Centromere localisation and function of Mis18 requires ‘Yippee‐like’ domain‐mediated oligomerisation. EMBO Rep 17: 496–507 · DOI
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Metadata
- Authors
- Spiller, F., Medina‐Pritchard, B., Abad, M. A., Wear, M. A., Molina, O., Earnshaw, W. C., & Jeyaprakash, A. A.
- Affiliations
- Wellcome Centre for Cell Biology (GB)
- Corresponding author
- Jeyaprakash, A Arockia
- ORCID
- Venue
- The EMBO Reports
- Published
- 2017-04-04
- Volume
- 18
- Issue
- 6
- Pages
- 894-905
- ISSN
- 1469-221X (ISSN-L)
- 1469-3178
- PMC
- PMC5452045
- OpenAlex
- W2604187656
- Cited by
- 66
- References
- 33
- Citations by year
- 2026: 7 · 2025: 7 · 2024: 8 · 2023: 8 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 6 · 2018: 6 · 2017: 3
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- EMBO Reports (publishedVersion, other-oa)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, cc-by)
- Funders
- Wellcome Trust (095822, 202811, 073915, 092076, 203149, 091020, 101527/Z/13/Z)
- European Commission (334291)
- 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 › Biochemistry, Genetics and Molecular Biology › Genetics › Chromosomal and Genetic Variations
- Keywords
- HJURP, centromere maintenance, CDK1 phosphorylation, protein complex formation, oligomerization, cell cycle regulation, centromeric nucleosomes
- MeSH terms
- Centromere Protein A, Cell Cycle, Centromere, Chromosomal Proteins, Non-Histone, DNA-Binding Proteins, Gene Expression Regulation, Humans, Nucleosomes, Phosphorylation, Protein Binding, CDC2 Protein Kinase, Adaptor Proteins, Signal Transducing
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