ArticleOncotarget2016
SIRT1 and LSD1 competitively regulate KU70 functions in DNA repair and mutation acquisition in cancer cells.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Molecular Sentinels: Unveiling the Role of Sirtuins in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Loss of SIRT1 inhibits hematopoietic stem cell aging and age-dependent mixed phenotype acute leukemia.Communications biology · 2022Article
- Involvement of classic and alternative non-homologous end joining pathways in hematologic malignancies: targeting strategies for treatment.Experimental hematology & oncology · 2021Review
- HOTAIR lncRNA promotes epithelial-mesenchymal transition by redistributing LSD1 at regulatory chromatin regions.EMBO reports · 2021Article
- Cytoplasmic-translocated Ku70 senses intracellular DNA and mediates interferon-lambda1 induction.Immunology · 2021Article
- SIRT1 and gynecological malignancies (Review).Oncology reports · 2021Review
- Post-Translational Modifications That Drive Prostate Cancer Progression.Biomolecules · 2021Review
- The Critical Role of SIRT1 in Parkinson's Disease: Mechanism and Therapeutic Considerations.Aging and disease · 2020Review
- NADSignal transduction and targeted therapy · 2020Review
- CMH-Small Molecule Docks into SIRT1, Elicits Human IPF-Lung Fibroblast Cell Death, Inhibits Ku70-deacetylation, FLIP and Experimental Pulmonary Fibrosis.Biomolecules · 2020Article
- Epigenetics and genome stability.Mammalian genome : official journal of the International Mammalian Genome Society · 2020Review
- CSL controls telomere maintenance and genome stability in human dermal fibroblasts.Nature communications · 2019Article
- Stability and sub-cellular localization of DNA polymerase β is regulated by interactions with NQO1 and XRCC1 in response to oxidative stress.Nucleic acids research · 2019Article
- The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer.International journal of molecular sciences · 2019Review
- Role of SIRT1 in hematologic malignancies.Journal of Zhejiang University. Science. B · 2019Review
- Apoptosis Induction byHistone Deacetylase Inhibitors in Cancer Cells: Role of Ku70.International journal of molecular sciences · 2019Review
- Epigenetic buffering of proteotoxic stress by EHMT2 enables meningioma growth.Neuro-oncology advancesArticle
- Lysine-specific demethylase 1 as a therapeutic cancer target: observations from preclinical study.Expert opinion on therapeutic targetsArticle
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Acquisition of BCR-ABL mutations underlies drug resistance of chronic myeloid leukemia (CML) to tyrosine kinase inhibitors, but the molecular mechanisms of mutation acquisition are poorly understood. We previously showed that lysine deacetylase sirtuin 1, SIRT1, promotes acquisition of BCR-ABL mutations in association with enhancing KU70 mediated non-homologous end joining DNA repair. In this study, we demonstrate that lysine specific demethylase 1 (LSD1) plays an opposite role to SIRT1 in regulating DNA repair and mutation acquisition. In response to therapeutic stress and DNA damage, LSD1 and SIRT1 compete for binding to KU70 on DNA damage foci globally and on the ABL locus. The recruitment of SIRT1 or LSD1 to KU70 impacts chromatin structure but does not correlate well with their direct histone modification functions, and SIRT1 helps maintain histone H4K16 acetylation and open chromatin for repair. The competitive KU70 binding by these proteins affects cancer cells' ability to repair broken DNA and acquire resistant genetic mutations in CML and prostate cancer cells. We identify that the core domain of KU70 binds both LSD1 and SIRT1, forming a molecular basis for the competition. The C-terminal SAP motif of KU70 mediates LSD1/SIRT1 competitive interaction by suppressing LSD1 binding to KU70 and ectopic expression of SAP-deleted KU70 to CML cells compromises their ability to acquire BCR-ABL mutations. Our study reveals a novel cellular stress response mechanism in cancer cells and a key role of LSD1/SIRT1/KU70 dynamic interaction in regulating DNA repair and mutation acquisition.
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Registered trials
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.