ArticleOncotarget2015
CCAR2/DBC1 is required for Chk2-dependent KAP1 phosphorylation and repair of DNA damage.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- miRNA-mediated cell-to-cell communications boost DNA repair during the radioadaptive response.Nucleic acids research · 2026Article
- Bone Metastatic Progression of Prostate Cancer Is Regulated by TRIM28-LDHA-Mediated Metabolism.Molecular cancer research : MCR · 2026Article
- Daxx-Dependent H3.3 Deposition Promotes Double-Strand Breaks Repair by Homologous Recombination.Cells · 2026Article
- SRSF3-TRIM28-MDC1 prevents DNA damage caused by R-loops in fatty liver disease in mice.JCI insight · 2026Article
- Phase 1 studies of the indenoisoquinolines LMP776 and LMP744 in patients with solid tumors and lymphomas.Cancer chemotherapy and pharmacology · 2025Article
- R-loops and impaired autophagy trigger cGAS-dependent inflammation via micronuclei formation in Senataxin-deficient cells.Cellular and molecular life sciences : CMLS · 2024Article
- Multifaceted roles of CCAR family proteins in the DNA damage response and cancer.Experimental & molecular medicine · 2024Review
- TRIM28 in cancer and cancer therapy.Frontiers in genetics · 2024Review
- Mechanistic insights into the dual role of CCAR2/DBC1 in cancer.Experimental & molecular medicine · 2023Review
- Sex specific regulation of TSPY-Like 2 in the DNA damage response of cancer cells.Cell death & disease · 2023Article
- Article
- Targeting the DNA Damage Response to Increase Anthracycline-Based Chemotherapy Cytotoxicity in T-Cell Lymphoma.International journal of molecular sciences · 2022Article
- CCAR1 and CCAR2 as gene chameleons with antagonistic duality: Preclinical, human translational, and mechanistic basis.Cancer science · 2020Review
- The Role of SIRT1 on DNA Damage Response and Epigenetic Alterations in Cancer.International journal of molecular sciences · 2019Review
- TSPYL2 is a novel regulator of SIRT1 and p300 activity in response to DNA damage.Cell death and differentiation · 2019Article
- Acetylation of CCAR2 Establishes a BET/BRD9 Acetyl Switch in Response to Combined Deacetylase and Bromodomain Inhibition.Cancer research · 2019Article
- The complexity of TRIM28 contribution to cancer.Journal of biomedical science · 2017Review
- A novel crosstalk between CCAR2 and AKT pathway in the regulation of cancer cell proliferation.Cell death & disease · 2016Article
- A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection.Nature communications · 2016Article
- Serial interactome capture of the human cell nucleus.Nature communications · 2016Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell cycle and apoptosis regulator 2 (CCAR2, formerly known as DBC1) is a nuclear protein largely involved in DNA damage response, apoptosis, metabolism, chromatin structure and transcription regulation. Upon DNA lesions, CCAR2 is phosphorylated by the apical kinases ATM/ATR and this phosphorylation enhances CCAR2 binding to SIRT1, leading to SIRT1 inhibition, p53 acetylation and p53-dependent apoptosis. Recently, we found that also the checkpoint kinase Chk2 and the proteasome activator REGγ are required for efficient CCAR2-mediated inhibition of SIRT1 and induction of p53-dependent apoptosis.Here, we report that CCAR2 is required for the repair of heterochromatic DNA lesions, as cells knock-out for CCAR2 retain, at late time-points after genotoxic treatment, abnormal levels of DNA damage-associated nuclear foci, whose timely resolution is reinstated by HP1β depletion. Conversely, repair of DNA damages in euchromatin are not affected by CCAR2 absence.We also report that the impairment in heterochromatic DNA repair is caused by defective Chk2 activation, detectable in CCAR2 ablated cells, which finally impacts on the phosphorylation of the Chk2 substrate KAP1 that is required for the induction of heterochromatin relaxation and DNA repair.These studies further extend and confirm the role of CCAR2 in the DNA damage response and DNA repair and illustrate a new mechanism of Chk2 activity regulation. Moreover, the involvement of CCAR2 in the repair of heterochromatic DNA breaks suggests a new role for this protein in the maintenance of chromosomal stability, which is necessary to prevent cancer formation.
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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.