i.e. A12B4C3, a potent, noncompetitive inhibitor of the phosphatase activity of human polynucleotide kinase/phosphatase in vitro. The inhibitor can form a ternary complex with PNKP and a DNA substrate, the inhibitor does not prevent DNA from binding to the phosphatase DNA binding site, but disrupts the secondary structure of PNKP, interaction between Trp402 of PNKP and the inhibitor. A12B4C3 sensitizes A549 human lung cancer cells to the topoisomerase I poison, camptothecin, but not the topoisomerase II poison, etoposide, in a manner similar to small interferingRNAagainst PNKP
A Novel Homozygous Variant in the Fork-Head-Associated Domain of Polynucleotide Kinase Phosphatase in a Patient Affected by Late-Onset Ataxia With Oculomotor Apraxia Type 4.
The RIR motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.
A Novel Homozygous Variant in the Fork-Head-Associated Domain of Polynucleotide Kinase Phosphatase in a Patient Affected by Late-Onset Ataxia With Oculomotor Apraxia Type 4.
The RIR motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.
A synthetically lethal nanomedicine delivering novel inhibitors of polynucleotide kinase 3'-phosphatase (PNKP) for targeted therapy of PTEN-deficient colorectal cancer.
The human polynucleotide kinase/phosphatase (hPNKP) inhibitor A12B4C3 radiosensitizes human myeloid leukemia cells to Auger electron-emitting anti-CD123 (111)In-NLS-7G3 radioimmunoconjugates.
A Novel Homozygous Variant in the Fork-Head-Associated Domain of Polynucleotide Kinase Phosphatase in a Patient Affected by Late-Onset Ataxia With Oculomotor Apraxia Type 4.
The RIR motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.
A synthetically lethal nanomedicine delivering novel inhibitors of polynucleotide kinase 3'-phosphatase (PNKP) for targeted therapy of PTEN-deficient colorectal cancer.
The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy.
The RIR motif in the scaffold protein XRCC1 mediates a low-affinity interaction with polynucleotide kinase/phosphatase (PNKP) during DNA single-strand break repair.
genotype variant NKP T5644G in polynucleotide kinase 3' phosphatase (PNKP) and risk of adenoma recurrence analyzed by unconditional logistic regression models, SNP genotyping, allele-specific PCR and mass spectromety, no association or effect modification between genotype, dietary components and risk of adenoma recurrence, PNKP T5644G variant not involved in adenoma recurrence
PNKP function is modulated by interaction with the DNA repair scaffold proteins XRCC1 and XRCC4, which is mediated by binding of the PNKP FHA domain to phosphorylated motifs on XRCC1 and XRCC4, overview
mutations that lead to alterations in PNKP, similar to mutations in genes encoding other strand break repair proteins, are associated with a severe autosomal recessive neurological disorder
aprataxin polynucleotide kinase/phosphatase-like factor (APLF) facilitates nonhomologous end joining (NHEJ) and associates with the core NHEJ components XRCC4-DNA ligase IV and Ku. The APLF-Ku interaction is functionally important in DNA repair and may be important for APLF stability
polynucleotide kinase/phosphatase serves a crucial role in the repair of DNA strand breaks by catalyzing the restoration of 5'-phosphate and 3'-hydroxyl termini. It is involved in single-strand break repair and participates in several DNA repair pathways through interactions with other DNA repair proteins, notably XRCC1 and XRCC4, regulation and enzyme recruitment, overview. Physiological importance of PNKP in maintaining the genomic stability of normal tissues, particularly developing neural cells, as well as enhancing the resistance of cancer cells to genotoxic therapeutic agents. The enzyme also performs base excision and double-strand break repair, overview
PNKP stably associates with ataxin-3. Purified wild-type ataxin-3 stimulates, and the mutant form specifically inhibits, PNKP's 3'-phosphatase activity in vitro. ATXN3-deficient cells also show decreased PNKP activity
PNK phosphatase is a multidomain enzyme that consists of an N-terminal forkhead-associated domain and a C-terminal catalytic domain composed of fused phosphatase and kinase subdomains, structure of mammalian PNK phosphatase, overview
kinase negative PNKP is generated by site-directed mutagenesis using RNAi-resistant PNKP cDNA. Phosphatase negative PNKP is generated by site-directed mutagenesis using RNAi-resistant PNKP cDNA, enzyme-deficient A-549 cells are constructed by expression of shRNA
expression of N-or C-terminally His-tagged enzyme in A-549 cells, expression of N-terminally His-tagged wild-type and mutant enzymes in Escherichia coli
human Machado-Joseph disease patients' brain samples show a significant accumulation of DNA strand breaks. PNKP stably associates with ataxin-3, a polyglutamine repeat-containing protein mutated in spinocerebellar ataxia type 3, i.e. Machado-Joseph disease
PNKP, similar to several other DNA repair proteins, is of increasing clinical interest owing to the identification of small molecule inhibitors of these enzymes that sensitize cells to IR or chemotherapeutic agents
Molecular cloning of the human gene, PNKP, encoding a polynucleotide kinase 3-phosphatase and evidence for its role in repair of DNA strand breaks caused by oxidative damage
The interaction between polynucleotide kinase phosphatase and the DNA repair protein XRCC1 is critical for repair of DNA alkylation damage and stable association at DNA damage sites