ReviewAnti-cancer agents in medicinal chemistry2008
Polynucleotide kinase as a potential target for enhancing cytotoxicity by ionizing radiation and topoisomerase I inhibitors.
Review in Anti-cancer agents in medicinal chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 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
16 citing papers in PubMed, 36 citations in OpenAlex.
- CDK-dependent phosphorylation regulates PNKP function in DNA replication.The Journal of biological chemistry · 2024Article
- DNA double-strand break genetic variants in patients with premature ovarian insufficiency.Journal of ovarian research · 2023Review
- Nano-Delivery of a Novel Inhibitor of Polynucleotide Kinase/Phosphatase (PNKP) for Targeted Sensitization of Colorectal Cancer to Radiation-Induced DNA Damage.Frontiers in oncology · 2021Article
- Domain analysis of PNKP-XRCC1 interactions: Influence of genetic variants of XRCC1.The Journal of biological chemistry · 2019Article
- Article
- The effector AvrRxo1 phosphorylates NAD in planta.PLoS pathogens · 2017Article
- Characterization of DNA Substrate Binding to the Phosphatase Domain of the DNA Repair Enzyme Polynucleotide Kinase/Phosphatase.Biochemistry · 2017Article
- Gold(III) macrocycles: nucleotide-specific unconventional catalytic inhibitors of human topoisomerase I.Journal of the American Chemical Society · 2014Article
- Structural basis for the phosphatase activity of polynucleotide kinase/phosphatase on single- and double-stranded DNA substrates.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Phosphorylation of polynucleotide kinase/ phosphatase by DNA-dependent protein kinase and ataxia-telangiectasia mutated regulates its association with sites of DNA damage.Nucleic acids research · 2011Article
- Tidying up loose ends: the role of polynucleotide kinase/phosphatase in DNA strand break repair.Trends in biochemical sciences · 2011Review
- Dual modes of interaction between XRCC4 and polynucleotide kinase/phosphatase: implications for nonhomologous end joining.The Journal of biological chemistry · 2010Article
- Mechanism of action of an imidopiperidine inhibitor of human polynucleotide kinase/phosphatase.The Journal of biological chemistry · 2010Article
- The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway.Annual review of biochemistry · 2010Review
- Hitting the bull's eye: novel directed cancer therapy through helicase-targeted synthetic lethality.Journal of cellular biochemistry · 2009Review
- Repair of ionizing radiation-induced DNA double-strand breaks by non-homologous end-joining.The Biochemical journal · 2009Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cytotoxicity of many antineoplastic agents is due to their capacity to damage DNA and there is evidence indicating that DNA repair contributes to the cellular resistance to such agents. DNA strand breaks constitute a significant proportion of the lesions generated by a broad range of genotoxic agents, either directly, or during the course of DNA repair. Strand breaks that are caused by many agents including ionizing radiation, topoisomerase I inhibitors, and DNA repair glycosylases such as NEIL1 and NEIL2, often contain 5'-hydroxyl and/or 3'-phosphate termini. These ends must be converted to 5'-phosphate and 3'-hydroxyl termini in order to allow DNA polymerases and ligases to catalyze repair synthesis and strand rejoining. A key enzyme involved in this end-processing is polynucleotide kinase (PNK), which possesses two enzyme activities, a DNA 5'-kinase activity and a 3'-phosphatase activity. PNK participates in the single-strand break repair pathway and the non-homologous end joining pathway for double-strand break repair. RNAi-mediated down-regulation of PNK renders cells more sensitive to ionizing radiation and camptothecin, a topoisomerase I inhibitor. Structural analysis of PNK revealed the protein is composed of three domains, the kinase domain at the C-terminus, the phosphatase domain in the centre and a forkhead associated (FHA) domain at the N-terminus. The FHA domain plays a critical role in the binding of PNK to other DNA repair proteins. Thus each PNK domain may be a suitable target for small molecule inhibition to effectively reduce resistance to ionizing radiation and topoisomerase I inhibitors.
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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.