論文 - 詳細
| RRC ID | 83162 |
|---|---|
| 著者 | Lim KK, Lam UTF, Li Y, Zeng YB, Yang H, Chen ES. |
| タイトル | Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A. |
| ジャーナル | Nucleic Acids Res |
| Abstract |
Precise positioning of the histone-H3 variant, CENP-A, ensures centromere stability and faithful chromosomal segregation. Mislocalization of CENP-A to extra-centromeric loci results in aneuploidy and compromised cell viability associated with formation of ectopic kinetochores. The mechanism that retargets mislocalized CENP-A back to the centromere is unclarified. We show here that the downregulation of the histone H3 lysine 36 (H3K36) methyltransferase Set2 can preserve centromere localization of a temperature-sensitive mutant cnp1-1 Schizosaccharomyces pombe CENP-A (SpCENP-A) protein and reverse aneuploidy by redirecting mislocalized SpCENP-A back to centromere from ribosomal DNA (rDNA) loci, which serves as a sink for the delocalized SpCENP-A. Downregulation of set2 augments Swc2 (SWR1 complex DNA-binding module) expression and releases histone chaperone Ccp1 from the centromeric reservoir. Swc2 and Ccp1 are directed to the rDNA locus to excavate the SpCENP-Acnp1-1, which is relocalized to the centromere in a manner dependent on canonical SpCENP-A loaders, including Mis16, Mis17 and Mis18, thereby conferring cell survival and safeguarding chromosome segregation fidelity. Chromosome missegregation is a severe genetic instability event that compromises cell viability. This mechanism thus promotes CENP-A presence at the centromere to maintain genomic stability. |
| 巻・号 | 52(8) |
| ページ | 4198-4214 |
| 公開日 | 2024-5-8 |
| DOI | 10.1093/nar/gkae084 |
| PII | 7619541 |
| PMID | 38442274 |
| PMC | PMC11077061 |
| MeSH | Aneuploidy Centromere* / metabolism Centromere Protein A* / genetics Centromere Protein A* / metabolism Chromosomal Proteins, Non-Histone* / genetics Chromosomal Proteins, Non-Histone* / metabolism Chromosome Segregation DNA, Ribosomal / genetics DNA, Ribosomal / metabolism DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism Histone Chaperones / metabolism Histone-Lysine N-Methyltransferase / genetics Histone-Lysine N-Methyltransferase / metabolism Histones / genetics Histones / metabolism Kinetochores / metabolism Schizosaccharomyces* / genetics Schizosaccharomyces* / metabolism Schizosaccharomyces pombe Proteins* / genetics Schizosaccharomyces pombe Proteins* / metabolism |
| IF | 11.502 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 各媒体での言及数の合計 | 0 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 酵母 | FY11202 FY21235 FY21234 FY20045 FY20043 FY20039 |