ArticleNucleic acids research2020
The deacetylase SIRT6 promotes the repair of UV-induced DNA damage by targeting DDB2.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- Emerging roles of SIRT6 and its modulators in kidney diseases.Cell death discovery · 2026Review
- Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.MedComm · 2026Review
- Dynamic regulation of TBK1 lactylation shapes antiviral immune responses.Cellular & molecular immunology · 2026Article
- ACSL5 Regulates Glucose Metabolism and Chemotherapy Sensitivity in Colorectal Cancer Cells under Glutamine Deficiency.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- 2. Diagnosis and Classification of Diabetes: Standards of Care in Diabetes-2026.Diabetes care · 2026Review
- SIRT6 activation relieves neuropathic pain by restoring Nrf2 signaling and inhibiting NLRP3 inflammasome.Frontiers in physiology · 2026Article
- Clinical Age-reversal Quantification of a Facial Skincare Regimen with Sirtuin-targeting Ingredients in a Multiethnic Population.The Journal of clinical and aesthetic dermatology · 2025Article
- SIRT6 in Cancer: Mechanistic Insights into Its Dual Roles in Cancer Biology and Implications for Precision Therapeutic Development.Biomolecules · 2025Review
- Downregulation of ZFP36L1 contributes to methotrexate resistance in osteosarcoma through enhanced NHEJ DNA repair mechanisms.Cell death & disease · 2025Article
- The association of the SIRT6 rs117385980 variant with frailty and longevity: an exploratory study.Scientific reports · 2025Article
- Targeting DNA damage in ageing: towards supercharging DNA repair.Nature reviews. Drug discovery · 2025Review
- Chlorogenic acid targets SIRT6 to relieve UVB - induced UV damage.Archives of dermatological research · 2025Article
- hnRNPA2B1 deacetylation by SIRT6 restrains local transcription and safeguards genome stability.Cell death and differentiation · 2025Article
- The advances in acetylation modification in senescence and aging-related diseases.Frontiers in physiology · 2025Review
- Review
- The type of DNA damage response after decitabine treatment depends on the level of DNMT activity.Life science alliance · 2024Article
- SIRT2 promotes base excision repair by transcriptionally activating OGG1 in an ATM/ATR-dependent manner.Nucleic acids research · 2024Article
- Sirt6 regulates the proliferation of neural precursor cells and cortical neurogenesis in mice.iScience · 2024Article
- Activation of SIRT6 Deacetylation by DNA Strand Breaks.ACS omega · 2023Article
- Functional Diversity of SIRT7 Across Cellular Compartments: Insights and Perspectives.Cell biochemistry and biophysics · 2023Review
Corrections and comments
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Authors and funding
13 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The NAD+-dependent deacetylase and mono-ADP-ribosyl transferase SIRT6 stabilizes the genome by promoting DNA double strand break repair, thereby acting as a tumor suppressor. However, whether SIRT6 regulates nucleotide excision repair (NER) remains unknown. Here, we showed that SIRT6 was recruited to sites of UV-induced DNA damage and stimulated the repair of UV-induced DNA damage. Mechanistic studies further indicated that SIRT6 interacted with DDB2, the major sensor initiating global genome NER (GG-NER), and that the interaction was enhanced upon UV irradiation. SIRT6 deacetylated DDB2 at two lysine residues, K35 and K77, upon UV stress and then promoted DDB2 ubiquitination and segregation from chromatin, thereby facilitating downstream signaling. In addition, we characterized several SIRT6 mutations derived from melanoma patients. These SIRT6 mutants ablated the stimulatory effect of SIRT6 on NER and destabilized the genome due to (i) partial loss of enzymatic activity (P27S or H50Y), (ii) a nonsense mutation (R150*) or (iii) high turnover rates (G134W). Overall, we demonstrate that SIRT6 promotes NER by deacetylating DDB2, thereby preventing the onset of melanomagenesis.
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Registered trials
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