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. Jilani, A., Ramotar, D., Slack, C., Ong, C., Yang, X. M., Scherer, S. W., & Lasko, D. D. The Journal of Biological Chemistry, 274(34):24176–24186, August, 1999.
abstract   bibtex   
Mammalian polynucleotide kinases catalyze the 5'-phosphorylation of nucleic acids and can have associated 3'-phosphatase activity, predictive of an important function in DNA repair following ionizing radiation or oxidative damage. The sequences of three tryptic peptides from a bovine 60-kDa polypeptide that correlated with 5'-DNA kinase and 3'-phosphatase activities identified human and murine dbEST clones. The 57.1-kDa conceptual translation product of this gene, polynucleotide kinase 3'-phosphatase (PNKP), contained a putative ATP binding site and a potential 3'-phosphatase domain with similarity to L-2-haloacid dehalogenases. BLAST searches identified possible homologs in Caenorhabditis elegans, Schizosaccharomyces pombe, and Drosophila melanogaster. The gene was localized to chromosome 19q13.3-13.4. Northern analysis indicated a 2-kilobase mRNA in eight human tissues. A glutathione S-transferase-PNKP fusion protein displayed 5'-DNA kinase and 3'-phosphatase activities. PNKP is the first gene for a DNA-specific kinase from any organism. PNKP expression partially rescued the sensitivity to oxidative damaging agents of the Escherichia coli DNA repair-deficient xth nfo double mutant. PNKP gene function restored termini suitable for DNA polymerase, consistent with in vivo removal of 3'-phosphate groups, facilitating DNA repair.
@article{jilani_molecular_1999,
	title = {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},
	volume = {274},
	issn = {0021-9258},
	abstract = {Mammalian polynucleotide kinases catalyze the 5'-phosphorylation of nucleic acids and can have associated 3'-phosphatase activity, predictive of an important function in DNA repair following ionizing radiation or oxidative damage. The sequences of three tryptic peptides from a bovine 60-kDa polypeptide that correlated with 5'-DNA kinase and 3'-phosphatase activities identified human and murine dbEST clones. The 57.1-kDa conceptual translation product of this gene, polynucleotide kinase 3'-phosphatase (PNKP), contained a putative ATP binding site and a potential 3'-phosphatase domain with similarity to L-2-haloacid dehalogenases. BLAST searches identified possible homologs in Caenorhabditis elegans, Schizosaccharomyces pombe, and Drosophila melanogaster. The gene was localized to chromosome 19q13.3-13.4. Northern analysis indicated a 2-kilobase mRNA in eight human tissues. A glutathione S-transferase-PNKP fusion protein displayed 5'-DNA kinase and 3'-phosphatase activities. PNKP is the first gene for a DNA-specific kinase from any organism. PNKP expression partially rescued the sensitivity to oxidative damaging agents of the Escherichia coli DNA repair-deficient xth nfo double mutant. PNKP gene function restored termini suitable for DNA polymerase, consistent with in vivo removal of 3'-phosphate groups, facilitating DNA repair.},
	language = {eng},
	number = {34},
	journal = {The Journal of Biological Chemistry},
	author = {Jilani, A. and Ramotar, D. and Slack, C. and Ong, C. and Yang, X. M. and Scherer, S. W. and Lasko, D. D.},
	month = aug,
	year = {1999},
	keywords = {Amino Acid Sequence, Animals, Base Sequence, Blotting, Southern, Cattle, Chromosome Mapping, Cloning, Molecular, DNA Damage, DNA Repair, DNA, Complementary, Humans, Hydrogen Peroxide, Molecular Sequence Data, Oxidation-Reduction, Phosphoric Monoester Hydrolases, Polynucleotide 5'-Hydroxyl-Kinase},
	pages = {24176--24186},
}

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