ArticleOncotarget2015
Gastric cancer associated variant of DNA polymerase beta (Leu22Pro) promotes DNA replication associated double strand breaks.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- Hyperactivation of the cGAS-STING pathway promotes liver inflammation in Down syndrome.Genes and immunity · 2026Article
- DRP lyase deficient DNA polymerase beta impairs mitochondrial electron transport chain and compromise mitochondrial DNA integrity.Research square · 2026Article
- 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
- Inhibition of DHODH Enhances Replication-Associated Genomic Instability and Promotes Sensitivity in Endometrial Cancer.Cancers · 2023Article
- Human Polβ Natural Polymorphic Variants G118V and R149I Affects Substate Binding and Catalysis.International journal of molecular sciences · 2023Article
- Repurposing Benztropine, Natamycin, and Nitazoxanide Using Drug Combination and Characterization of Gastric Cancer Cell Lines.Biomedicines · 2023Article
- Proteomic signatures of infiltrative gastric cancer by proteomic and bioinformatic analysis.World journal of gastrointestinal oncology · 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
- Defective DNA polymerase beta invoke a cytosolic DNA mediated inflammatory response.Frontiers in immunology · 2022Article
- Mutation in DNA Polymerase Beta Causes Spontaneous Chromosomal Instability and Inflammation-Associated Carcinogenesis in Mice.Cancers · 2019Article
- Reactivity and Cross-Linking of 5'-Terminal Abasic Sites within DNA.Chemical research in toxicology · 2017Article
- R152C DNA Pol β mutation impairs base excision repair and induces cellular transformation.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
DNA polymerase beta (Pol β) is a key enzyme for the protection against oxidative DNA lesions via its role in base excision repair (BER). Approximately 1/3 of tumors studied to date express Pol β variant proteins, and several tumors overexpress Pol β. Pol β possesses DNA polymerase and dRP lyase activities, both of which are known to be important for efficient BER. The dRP lyase activity resides within the 8kDa amino terminal domain of Pol β, is responsible for removal of the 5' phosphate group (5'-dRP). The DNA polymerase subsequently fills the gaps. Previously, we demonstrated that the human gastric cancer-associated variant of Pol β (Leu22Pro (L22P)) lacks dRP lyase function in vitro. Here, we report that L22P-expressing cells harbor significantly increased replication associated DNA double strand breaks (DSBs) and defective maintenance of the nascent DNA strand (NDS) during replication stress. Moreover, L22P-expressing cells are sensitive to PARP1 inhibitors, which suggests trapped PARP1 binds to the 5'-dRP group and blocks replications forks, resulting in fork collapse and DSBs. Our data suggest that the normal function of the dRP lyase is critical to maintain replication fork integrity and prevent replication fork collapse to DSBs and cellular transformation.
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