ArticleNature structural & molecular biology2016
SIRT6 deacetylates H3K18ac at pericentric chromatin to prevent mitotic errors and cellular senescence.
Article in Nature structural & molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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140 citing papers in PubMed, 213 citations in OpenAlex.
- Critical role of Sirtuin 6 (SIRT6) in osteoarthritis chondrocytes: the interaction among various biological processes.Annals of medicine · 2026Review
- Article
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Conserved Transcriptomic Signatures of Sirt6 Activity: A Cross-Species RNA-seq Meta-analysis.bioRxiv : the preprint server for biology · 2026Article
- Facile Synthesis of H-L-Photo-Lysine and Its Genetic Incorporation Into Proteins.Chembiochem : a European journal of chemical biology · 2026Article
- Lactate metabolism and lactylation in cancer: from pathogenesis to therapeutic advances.Signal transduction and targeted therapy · 2026Review
- SIRT6 overexpression counteracts chromatin aging in the male murine liver.Nature communications · 2026Article
- Role of Sirtuin 6 in the Pathogenesis of Metabolic Dysfunction-Associated Steatotic Liver Disease.Current issues in molecular biology · 2026Review
- SIRT6 cooperates with KDM5C to transcriptionally silence MICAL2 and inhibit tumorigenesis in pancreatic cancer.Cell communication and signaling : CCS · 2026Article
- Kinetic Analysis of HDAC- and Sirtuin-Mediated Deacylation on Chemically Defined Histones and Nucleosomes.Current protocols · 2025Article
- Antibiotics induce overexpression of alpha satellite DNA accompanied with epigenetic changes at alpha satellite arrays as well as genome-wide.Epigenetics & chromatin · 2025Article
- Structural and enzymatic plasticity of SIRT6 deacylase activity.The Journal of biological chemistry · 2025Article
- Sirt6 loss activates Got1 and facilitates cleft palate through abnormal activating glycolysis.Cell death & disease · 2025Article
- Structural Insights Into centSIRT6: Bioinformatic Analysis of N308K and A313S Substitution Effects.Bioinformatics and biology insights · 2025Article
- The age-related decline of helicase function-how G-quadruplex structures promote genome instability.FEBS letters · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- Research advances on silence information regulator 6 as a potential therapeutic target for bone regeneration and repair.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- Epigenetic and transcriptional control of adipocyte function by centenarian-associated SIRT6 N308K/A313S mutant.Clinical epigenetics · 2024Article
- Oncogenic ETS fusions promote DNA damage and proinflammatory responses via pericentromeric RNAs in extracellular vesicles.The Journal of clinical investigation · 2024Article
- Discovery of a potent and highly selective inhibitor of SIRT6 against pancreatic cancer metastasisActa pharmaceutica Sinica. B · 2024Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Pericentric heterochromatin silencing at mammalian centromeres is essential for mitotic fidelity and genomic stability. Defective pericentric silencing has been observed in senescent cells, aging tissues, and mammalian tumors, but the underlying mechanisms and functional consequences of these defects are unclear. Here, we uncover an essential role of the human SIRT6 enzyme in pericentric transcriptional silencing, and we show that this function protects against mitotic defects, genomic instability, and cellular senescence. At pericentric heterochromatin, SIRT6 promotes deacetylation of a new substrate, residue K18 of histone H3 (H3K18), and inactivation of SIRT6 in cells leads to H3K18 hyperacetylation and aberrant accumulation of pericentric transcripts. Strikingly, depletion of these transcripts through RNA interference rescues the mitotic and senescence phenotypes of SIRT6-deficient cells. Together, our findings reveal a new function for SIRT6 and regulation of acetylated H3K18 at heterochromatin, and demonstrate the pathogenic role of deregulated pericentric transcription in aging- and cancer-related cellular dysfunction.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.