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https://doi.org/10.1093/nar/gkae084
Title: | Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A. | Authors: | Lim, Kim Kiat Lam, Ulysses Tsz Fung Li, Ying Zeng, Yi Bing Yang, Henry Chen, Ee Sin |
Issue Date: | 5-Mar-2024 | Publisher: | Oxford University Press (OUP) | Citation: | Lim, Kim Kiat, Lam, Ulysses Tsz Fung, Li, Ying, Zeng, Yi Bing, Yang, Henry, Chen, Ee Sin (2024-03-05). Set2 regulates Ccp1 and Swc2 to ensure centromeric stability by retargeting CENP-A. : gkae084-. ScholarBank@NUS Repository. https://doi.org/10.1093/nar/gkae084 | 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. | URI: | https://scholarbank.nus.edu.sg/handle/10635/247594 | ISSN: | 0305-1048 1362-4962 |
DOI: | 10.1093/nar/gkae084 |
Appears in Collections: | Staff Publications Elements |
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2024 Lim et al NAR (Set2 Swc2 Ccp1).pdf | 2.31 MB | Adobe PDF | OPEN | Published | View/Download |
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