ArticleNucleic acids research2014
The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2'-deoxycytidine lesions.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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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
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 85 citations in OpenAlex.
- Prognostic and clinicopathological significance of GPRC5A in various cancers: A systematic review and meta-analysis.PloS one · 2021Pooled it
- DNA methyltransferase inhibitors in oncology: clinical progress, limitations and future directions.Epigenomics · 2026Review
- RRM1 inhibition sensitizes lung adenocarcinoma to decitabine treatment.Cell death & disease · 2026Article
- Poly (ADP-Ribose) Glycohydrolase-Dependent dePARylation of PCNA Is Essential for DNA Replication.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Article
- PARP inhibitor augments anti-tumor efficacy of DNMT inhibitor by inducing senescence in cholangiocarcinoma.International journal of biological sciences · 2025Article
- Impact of DNA ligase inhibition on the nick sealing of polβ nucleotide insertion products at the downstream steps of base excision repair pathway.Mutagenesis · 2024Article
- The type of DNA damage response after decitabine treatment depends on the level of DNMT activity.Life science alliance · 2024Article
- Decitabine cytotoxicity is promoted by dCMP deaminase DCTD and mitigated by SUMO-dependent E3 ligase TOPORS.The EMBO journal · 2024Article
- Advances in DNA damage response inhibitors in colorectal cancer therapy.Acta biochimica et biophysica Sinica · 2024Review
- Therapeutic targeting of PARP with immunotherapy in acute myeloid leukemia.Frontiers in pharmacology · 2024Review
- Triggering pyroptosis enhances the antitumor efficacy of PARP inhibitors in prostate cancer.Cellular oncology (Dordrecht, Netherlands) · 2023Article
- Acute Myeloid Leukemia Following Myeloproliferative Neoplasms: A Review of What We Know, What We Do Not Know, and Emerging Treatment Strategies.Journal of hematology · 2022Review
- Role of Cockayne Syndrome Group B Protein in Replication Stress: Implications for Cancer Therapy.International journal of molecular sciences · 2022Review
- Article
- Epigenetic Anti-Cancer Treatment With a Stabilized Carbocyclic Decitabine Analogue.Chemistry (Weinheim an der Bergstrasse, Germany) · 2022Article
- Article
- Targeting PARP proteins in acute leukemia: DNA damage response inhibition and therapeutic strategies.Journal of hematology & oncology · 2022Review
- OGG1 Inhibition Triggers Synthetic Lethality and Enhances The Effect of PARP Inhibitor Olaparib in BRCA1-Deficient TNBC Cells.Frontiers in oncology · 2022Article
- DNA Demethylation Switches Oncogenic ΔNp63 to Tumor Suppressive TAp63 in Squamous Cell Carcinoma.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Decitabine (5-aza-2'-deoxycytidine, 5-azadC) is used in the treatment of Myelodysplatic syndrome (MDS) and Acute Myeloid Leukemia (AML). Its mechanism of action is thought to involve reactivation of genes implicated in differentiation and transformation, as well as induction of DNA damage by trapping DNA methyltranferases (DNMT) to DNA. We demonstrate for the first time that base excision repair (BER) recognizes 5-azadC-induced lesions in DNA and mediates repair. We find that BER (XRCC1) deficient cells are sensitive to 5-azadC and display an increased amount of DNA single- and double-strand breaks. The XRCC1 protein co-localizes with DNMT1 foci after 5-azadC treatment, suggesting a novel and specific role of XRCC1 in the repair of trapped DNMT1. 5-azadC-induced DNMT foci persist in XRCC1 defective cells, demonstrating a role for XRCC1 in repair of 5-azadC-induced DNA lesions. Poly (ADP-ribose) polymerase (PARP) inhibition prevents XRCC1 relocation to DNA damage sites, disrupts XRCC1-DNMT1 co-localization and thereby efficient BER. In a panel of AML cell lines, combining 5-azadC and Olaparib cause synthetic lethality. These data suggest that PARP inhibitors can be used in combination with 5-azadC to improve treatment of MDS and AML.
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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.