Nucleic Acids Research, Vol 26, Issue 19 4395-4400, Copyright © 1998 by Oxford University Press
F Karimi-Busheri, J Lee, AE Tomkinson and M Weinfeld
A putative role for mammalian polynucleotide kinases that possess both
5'-phosphotransferase and 3'-phosphatase activity is the restoration of DNA
strand breaks with 5'-hydroxyl termini or 3'-phosphate termini, or both, to
a form that supports the subsequent action of DNA repair polymerases and
DNA ligases, i.e. 5'-phosphate and 3'-hydroxyl termini. To further assess
this possibility, we compared the activity of the 3'- phosphatase of
purified calf thymus polynucleotide kinase towards a variety of substrates.
The rate of removal of 3'-phosphate groups from nicked or short (1 nt)
gapped sites in double-stranded DNA was observed to be similar to that of
3'-phosphate groups from single-stranded substrates. Thus this activity of
polynucleotide kinase does not appear to be influenced by steric
accessibility of the phosphate group. We subsequently demonstrated that the
concerted reactions of polynucleotide kinase and purified human DNA ligase
I could efficiently repair DNA nicks possessing 3'-phosphate and
5'-hydroxyl termini, and similarly the combination of these two enzymes
together with purified rat DNA polymerase beta could seal a strand break
with a 1 nt gap. With a substrate containing a nick bounded by 3'- and
5'-OH termini, the rate of gap filling by polymerase beta was significantly
enhanced in the presence of polynucleotide kinase and ATP, indicating the
positive influence of 5'-phosphorylation. The reaction was further enhanced
by addition of DNA ligase I to the reaction mixture. This is due, at least
in part, to an enhancement by DNA ligase I of the rate of 5'-
phosphorylation catalyzed by polynucleotide kinase.
ARTICLES
Repair of DNA strand gaps and nicks containing 3'-phosphate and 5'- hydroxyl termini by purified mammalian enzymes
Experimental Oncology, Cross Cancer Institute, Department of Oncology, University of Alberta, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  R. S. Mani, M. Fanta, F. Karimi-Busheri, E. Silver, C. A. Virgen, K. W. Caldecott, C. E. Cass, and M. Weinfeld XRCC1 Stimulates Polynucleotide Kinase by Enhancing Its Damage Discrimination and Displacement from DNA Repair Intermediates J. Biol. Chem., September 21, 2007; 282(38): 28004 - 28013. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Karimi-Busheri, A. Rasouli-Nia, J. Allalunis-Turner, and M. Weinfeld Human Polynucleotide Kinase Participates in Repair of DNA Double-Strand Breaks by Nonhomologous End Joining but not Homologous Recombination Cancer Res., July 15, 2007; 67(14): 6619 - 6625. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Dobson and S. L. Allinson The phosphatase activity of mammalian polynucleotide kinase takes precedence over its kinase activity in repair of single strand breaks. Nucleic Acids Res., January 1, 2006; 34(8): 2230 - 2237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Rasouli-Nia, F. Karimi-Busheri, and M. Weinfeld Stable down-regulation of human polynucleotide kinase enhances spontaneous mutation frequency and sensitizes cells to genotoxic agents PNAS, May 4, 2004; 101(18): 6905 - 6910. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Puapaiboon, J. Jai-nhuknan, and J. A. Cowan Characterization of a multi-functional metal-mediated nuclease by MALDI-TOF mass spectrometry Nucleic Acids Res., September 1, 2001; 29(17): 3652 - 3656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jilani, D. Ramotar, C. Slack, C. Ong, X. M. Yang, S. W. Scherer, and D. D. Lasko 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 J. Biol. Chem., August 20, 1999; 274(34): 24176 - 24186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Karimi-Busheri, G. Daly, P. Robins, B. Canas, D. J. C. Pappin, J. Sgouros, G. G. Miller, H. Fakhrai, E. M. Davis, M. M. Le Beau, et al. Molecular Characterization of a Human DNA Kinase J. Biol. Chem., August 20, 1999; 274(34): 24187 - 24194. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Betti, S. Petrucco, A. Bolchi, G. Dieci, and S. Ottonello A Plant 3'-Phosphoesterase Involved in the Repair of DNA Strand Breaks Generated by Oxidative Damage J. Biol. Chem., May 18, 2001; 276(21): 18038 - 18045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Vance and T. E. Wilson Uncoupling of 3'-Phosphatase and 5'-Kinase Functions in Budding Yeast. CHARACTERIZATION OF SACCHAROMYCES CEREVISIAE DNA 3'-PHOSPHATASE (TPP1) J. Biol. Chem., April 27, 2001; 276(18): 15073 - 15081. [Abstract] [Full Text] [PDF]
|
|