ArticlePLoS genetics2012
A germline polymorphism of DNA polymerase beta induces genomic instability and cellular transformation.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 78 citations in OpenAlex.
- Biochemical, structural and mutational landscapes of base excision repair enzymes and cancer: from atomic resolution to tumor signatures.International journal of radiation biology · 2026Review
- Identifying Rare Germline Variants Associated with Metastatic Prostate Cancer Through an Extreme Phenotype Study.medRxiv : the preprint server for health sciences · 2025Article
- Repair pathway coordination from gap filling by polβ and subsequent nick sealing by LIG1 or LIG3α governs BER efficiency at the downstream steps.DNA repair · 2025Article
- Harnessing DNA polymerase beta defect enhances synthetic lethality and treatment response in gastric cancer cells: implication for immunotherapy.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025Review
- Aberrant DNA polymerase beta expression is associated with dysregulated tumor immune microenvironment and its prognostic value in gastric cancer.Clinical and experimental medicine · 2024Article
- Unfilled gaps by polβ lead to aberrant ligation by LIG1 at the downstream steps of base excision repair pathway.Nucleic acids research · 2024Article
- Mouse models to explore the biological and organismic role of DNA polymerase beta.Environmental and molecular mutagenesis · 2024Review
- DNA polymerase beta connects tumorigenicity with the circadian clock in liver cancer through the epigenetic demethylation of Per1.Cell death & disease · 2024Article
- Article
- Human Polβ Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis.International journal of molecular sciences · 2023Article
- A novel mechanism for macrophage pyroptosis in rheumatoid arthritis induced by Pol β deficiency.Cell death & disease · 2022Article
- Role of Base Excision Repair in Innate Immune Cells and Its Relevance for Cancer Therapy.Biomedicines · 2022Review
- The Role of Natural Polymorphic Variants of DNA Polymerase β in DNA Repair.International journal of molecular sciences · 2022Review
- Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis.BMC microbiology · 2021Review
- DNA polymerase β deficiency promotes the occurrence of esophageal precancerous lesions in mice.Neoplasia (New York, N.Y.) · 2021Review
- STING enhances cell death through regulation of reactive oxygen species and DNA damage.Nature communications · 2021Article
- Silencing DNA Polymerase β Induces Aneuploidy as a Biomarker of Poor Prognosis in Oral Squamous Cell Cancer.International journal of molecular sciences · 2021Article
- Review
- DNA polymerase beta modulates cancer progression via enhancing CDH13 expression by promoter demethylation.Oncogene · 2020Article
- The double-edged sword of cancer mutations: exploiting neoepitopes for the fight against cancer.Mutagenesis · 2020Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Several germline single nucleotide polymorphisms (SNPs) have been identified in the POLB gene, but little is known about their cellular and biochemical impact. DNA Polymerase β (Pol β), encoded by the POLB gene, is the main gap-filling polymerase involved in base excision repair (BER), a pathway that protects the genome from the consequences of oxidative DNA damage. In this study we tested the hypothesis that expression of the POLB germline coding SNP (rs3136797) in mammalian cells could induce a cancerous phenotype. Expression of this SNP in both human and mouse cells induced double-strand breaks, chromosomal aberrations, and cellular transformation. Following treatment with an alkylating agent, cells expressing this coding SNP accumulated BER intermediate substrates, including single-strand and double-strand breaks. The rs3136797 SNP encodes the P242R variant Pol β protein and biochemical analysis showed that P242R protein had a slower catalytic rate than WT, although P242R binds DNA similarly to WT. Our results suggest that people who carry the rs3136797 germline SNP may be at an increased risk for cancer susceptibility.
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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.