ArticleCancer research2010
Potentiation of temozolomide cytotoxicity by inhibition of DNA polymerase beta is accentuated by BRCA2 mutation.
Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Noncompetitive Inhibition of DNA Polymerase β by a Nonnative Nucleotide.The Journal of organic chemistry · 2025Review
- Obesity and cancer: A mechanistic overview of metabolic changes in obesity that impact genetic instability.Molecular carcinogenesis · 2019Review
- Translesion DNA Synthesis in Cancer: Molecular Mechanisms and Therapeutic Opportunities.Chemical research in toxicology · 2017Review
- DNA polymerase β contains a functional nuclear localization signal at its N-terminus.Nucleic acids research · 2017Article
- YU238259 Is a Novel Inhibitor of Homology-Dependent DNA Repair That Exhibits Synthetic Lethality and Radiosensitization in Repair-Deficient Tumors.Molecular cancer research : MCR · 2015Article
- Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.Cancer biology & therapy · 2015Article
- Exploiting base excision repair to improve therapeutic approaches for pancreatic cancer.Frontiers in nutrition · 2015Review
- Improved bioactivity of G-rich triplex-forming oligonucleotides containing modified guanine bases.Artificial DNA, PNA & XNA · 2014Article
- XPD-dependent activation of apoptosis in response to triplex-induced DNA damage.Nucleic acids research · 2013Article
- Sequence context modulation of polycyclic aromatic hydrocarbon-induced mutagenesis.Environmental and molecular mutagenesis · 2013Article
- Developing an in silico model of the modulation of base excision repair using methoxyamine for more targeted cancer therapeutics.IET systems biology · 2013Article
- Biological and therapeutic relevance of nonreplicative DNA polymerases to cancer.Antioxidants & redox signaling · 2013Review
- DNA damage tolerance: a double-edged sword guarding the genome.Translational cancer research · 2013Article
- Base excision repair and cancer.Cancer letters · 2012Review
- Targeting cancer with a lupus autoantibody.Science translational medicine · 2012Article
- S-phase sensing of DNA-protein crosslinks triggers TopBP1-independent ATR activation and p53-mediated cell death by formaldehyde.Cell cycle (Georgetown, Tex.) · 2012Article
- Balancing repair and tolerance of DNA damage caused by alkylating agents.Nature reviews. Cancer · 2012Review
- Transcriptional profiling reveals elevated Sox2 in DNA polymerase ß null mouse embryonic fibroblasts.American journal of cancer research · 2012Article
- Targeting DNA polymerase ß for therapeutic intervention.Current molecular pharmacology · 2012Review
- Two novel determinants of etoposide resistance in small cell lung cancer.Cancer research · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Base excision repair (BER) plays a critical role in the repair of bases damaged by oxidative metabolism or alkylating agents, such as those commonly used in cancer therapy. Incomplete BER generates intermediates that require activation of homology-dependent DNA repair to resolve. We investigated the effects of lithocholic acid (LCA), an inhibitor of the key BER enzyme DNA polymerase beta (pol beta), in cells deficient in expression of the homology-dependent repair factor BRCA2. In vitro studies show that LCA suppresses the DNA polymerase and 5'-deoxyribose phosphate lyase activities of DNA pol beta by preventing the formation of a stable pol beta-DNA complex, reducing BER effectiveness. Cytotoxicity assays based on colony formation revealed that LCA exhibits synergism with the alkylating agent temozolomide, which engages BER through DNA methylation, and that the degree of synergism is increased in cells lacking functional BRCA2. BRCA2-deficient cells also showed heightened susceptibility to both LCA and temozolomide individually. The potentiation of temozolomide cytotoxicity by LCA owes to the conversion of single-stranded DNA breaks generated through incomplete BER of methylated nucleotides into double-stranded breaks during DNA replication, as indicated by gammaH2AX immunofluorescence. Death seems to be induced in cotreated cells through an accumulation of persistent double-stranded DNA breaks. Mutations of the BRCA2 gene have been extensively characterized and are present in various cancers, implying that inhibition of BER may offer a means to augment tumor selectivity in the use of conventional cancer therapies.
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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.