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SKI regulates rRNA transcription and pericentromeric heterochromatin to ensure centromere integrity and genome stability

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dc.contributor.authorPola, Víctor
dc.contributor.authorCarrero, David
dc.contributor.authorSagredo, Eduardo
dc.contributor.authorInostroza, Víctor
dc.contributor.authorCappelli, Claudio
dc.contributor.authorRivas, Solange
dc.contributor.authorBitrán, Mirita
dc.contributor.authorZambrano, Evelyn
dc.contributor.authorGonzalez, Evelin
dc.contributor.authorMorales, Fernanda
dc.contributor.authorManterola, Marcia
dc.contributor.authorMontecino, Martín
dc.contributor.authorArmisen, Ricardo
dc.contributor.authorMarcelain, Katherine
dc.date.accessioned2025-07-04T17:05:12Z
dc.date.available2025-07-04T17:05:12Z
dc.date.issued2025
dc.description.abstractAccurate chromosome segregation and ribosomal gene expression silencing are essential for maintaining genome integrity, and disruptions in these processes are key for oncogenesis and cancer progression. Here, we demonstrate a novel role for the transcriptional co-repressor SKI in regulating rDNA and pericentromeric heterochromatin (PCH) silencing in human cells. We found that SKI localizes to the rDNA promoter on acrocentric chromosomes and is crucial for maintaining H3K9 trimethylation (H3K9me3) and repressing 45S rRNA gene expression. SKI is also associated with BSR and HSATII satellites within PCH, where is necessary for H3K9 methylation and recruitment of SUV39H1 and HP1α, key players for heterochromatin silencing and centromere function. Consequently, SKI deficiency disrupted centromere integrity and resulted in aberrant chromosome segregation, micronuclei formation, and chromosome instability. The identification of SKI as a key participant in the epigenetic-mediated silencing of pericentromeric and ribosomal DNA provides a fundamental insight, paving the way for new research into the intricate relationship between transcriptional regulation and genome instability during cancer progression, and opening novel opportunities for therapeutic intervention.
dc.description.versionVersión Publicada
dc.identifier.citationPola-Véliz V, Carrero D, Sagredo EA, Inostroza V, Cappelli C, Rivas S, Bitrán M, Zambrano E, Gonzalez E, Morales F, Manterola M, Montecino M, Armisén R, Marcelain K. SKI regulates rRNA transcription and pericentromeric heterochromatin to ensure centromere integrity and genome stability. Neoplasia. 2025 Jul 2;67:101204. doi: 10.1016/j.neo.2025.101204
dc.identifier.doihttps://doi.org/10.1016/j.neo.2025.101204
dc.identifier.urihttps://hdl.handle.net/11447/10116
dc.language.isoen
dc.subjectBreast cancer
dc.subjectChromosomal Instability
dc.subjectPericentromeric heterochromatin
dc.subjectSKI
dc.subjectrRNA
dc.titleSKI regulates rRNA transcription and pericentromeric heterochromatin to ensure centromere integrity and genome stability
dc.typeArticle
dcterms.accessRightsAcceso Abierto
dcterms.sourceNeoplasia: an international journal for oncology research
dspace.entity.typePublication
relation.isAuthorOfPublicationf814e5ac-2623-4a1f-bc2b-5a1a260ee316
relation.isAuthorOfPublication.latestForDiscoveryf814e5ac-2623-4a1f-bc2b-5a1a260ee316

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