Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability.
dc.contributor.author | Mishra, PK | en_US |
dc.contributor.author | Au, W-C | en_US |
dc.contributor.author | Castineira, PG | en_US |
dc.contributor.author | Ali, N | en_US |
dc.contributor.author | Stanton, J | en_US |
dc.contributor.author | Boeckmann, L | en_US |
dc.contributor.author | Takahashi, Y | en_US |
dc.contributor.author | Costanzo, M | en_US |
dc.contributor.author | Boone, C | en_US |
dc.contributor.author | Bloom, KS | en_US |
dc.contributor.author | Thorpe, PH | en_US |
dc.contributor.author | Basrai, MA | en_US |
dc.date.accessioned | 2024-01-16T12:28:02Z | |
dc.date.issued | 2023-09-01 | en_US |
dc.identifier.uri | https://qmro.qmul.ac.uk/xmlui/handle/123456789/93934 | |
dc.description.abstract | Centromere (CEN) identity is specified epigenetically by specialized nucleosomes containing evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully defined. In this study, we show that cell cycle-dependent methylation of Cse4-R37 regulates kinetochore function and high-fidelity chromosome segregation. We generated a custom antibody that specifically recognizes methylated Cse4-R37 and showed that methylation of Cse4 is cell cycle regulated with maximum levels of methylated Cse4-R37 and its enrichment at the CEN chromatin occur in the mitotic cells. Methyl-mimic cse4-R37F mutant exhibits synthetic lethality with kinetochore mutants, reduced levels of CEN-associated kinetochore proteins and chromosome instability (CIN), suggesting that mimicking the methylation of Cse4-R37 throughout the cell cycle is detrimental to faithful chromosome segregation. Our results showed that SPOUT methyltransferase Upa1 contributes to methylation of Cse4-R37 and overexpression of UPA1 leads to CIN phenotype. In summary, our studies have defined a role for cell cycle-regulated methylation of Cse4 in high-fidelity chromosome segregation and highlight an important role of epigenetic modifications such as methylation of kinetochore proteins in preventing CIN, an important hallmark of human cancers. | en_US |
dc.format.extent | ar99 - ? | en_US |
dc.language | eng | en_US |
dc.relation.ispartof | Mol Biol Cell | en_US |
dc.rights | This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/4.0). | |
dc.rights | Attribution 3.0 United States | * |
dc.rights.uri | http://creativecommons.org/licenses/by/3.0/us/ | * |
dc.subject | Humans | en_US |
dc.subject | Cell Cycle | en_US |
dc.subject | Centromere | en_US |
dc.subject | Centromere Protein A | en_US |
dc.subject | Chromosomal Instability | en_US |
dc.subject | Chromosomal Proteins, Non-Histone | en_US |
dc.subject | DNA-Binding Proteins | en_US |
dc.subject | Methylation | en_US |
dc.subject | Saccharomyces cerevisiae | en_US |
dc.subject | Saccharomyces cerevisiae Proteins | en_US |
dc.subject | Saccharomycetales | en_US |
dc.title | Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability. | en_US |
dc.type | Article | |
dc.rights.holder | © 2023 Mishra et al. | |
dc.identifier.doi | 10.1091/mbc.E23-03-0108 | en_US |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37436802 | en_US |
pubs.issue | 10 | en_US |
pubs.notes | Not known | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 34 | en_US |
rioxxterms.funder | Default funder | en_US |
rioxxterms.identifier.project | Default project | en_US |
qmul.funder | Master Regulation of Centromere Function by the Highly Conserved Mis18 Complex::Biotechnology and Biological Sciences Research Council | en_US |
qmul.funder | Master Regulation of Centromere Function by the Highly Conserved Mis18 Complex::Biotechnology and Biological Sciences Research Council | en_US |
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Except where otherwise noted, this item's license is described as This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial-Share Alike 4.0 International Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/4.0).