Published online 11 May 2004
Nucleic Acids Research, 2004, Vol. 32, No. 8 2550-2555
© 2004 Oxford University Press
XRCC1–DNA polymerase ß interaction is required for efficient base excision repair
1 Radiation and Genome Stability Unit, Medical Research Council, Harwell, Oxfordshire OX11 0RD, 2 Genome Damage and Stability Center, University of Sussex, Science Park Road, Falmer, Brighton BN1 9RQ and 3 Microbiology Department, University of Reading, Reading, UK
*To whom correspondence should be addressed. Tel: +44 1235 841 134; Fax: +44 1235 841 200; Email: g.dianov{at}har.mrc.ac.uk
Received April 2, 2004; Revised and Accepted April 5, 2004
X-ray repair cross-complementing protein-1 (XRCC1)-deficient cells are sensitive to DNA damaging agents and have delayed processing of DNA base lesions. In support of its role in base excision repair, it was found that XRCC1 forms a tight complex with DNA ligase III
and also interacts with DNA polymerase ß (Pol ß) and other base excision repair (BER) proteins. We have isolated wild-type XRCC1–DNA ligase III heterodimer and mutated XRCC1–DNA ligase III complex that does not interact with Pol ß and tested their activities in BER reconstituted with human purified proteins. We find that a point mutation in the XRCC1 protein which disrupts functional interaction with Pol ß, affected the ligation efficiency of the mutant XRCC1–DNA ligase III heterodimer in reconstituted BER reactions. We also compared sensitivity to hydrogen peroxide between wild-type CHO-9 cells, XRCC1-deficient EM-C11 cells and EM-C11 cells transfected with empty plasmid vector or with plasmid vector carrying wild-type or mutant XRCC1 gene and find that the plasmid encoding XRCC1 protein, that does not interact with Pol ß has reduced ability to rescue the hydrogen peroxide sensitivity of XRCC1- deficient cells. These data suggest an important role for the XRCC1–Pol ß interaction for coordinating the efficiency of the BER process.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N. P. Khairnar and H. S. Misra DNA polymerase X from Deinococcus radiodurans implicated in bacterial tolerance to DNA damage is characterized as a short patch base excision repair polymerase Microbiology, September 1, 2009; 155(9): 3005 - 3014. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Breslin and K. W. Caldecott DNA 3'-Phosphatase Activity Is Critical for Rapid Global Rates of Single-Strand Break Repair following Oxidative Stress Mol. Cell. Biol., September 1, 2009; 29(17): 4653 - 4662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Guo, L. Zheng, H. Dai, M. Zhou, H. Xu, and B. Shen Human DNA polymerase {beta} polymorphism, Arg137Gln, impairs its polymerase activity and interaction with PCNA and the cellular base excision repair capacity Nucleic Acids Res., June 1, 2009; 37(10): 3431 - 3441. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Prasad, S. S. Wallace, and D. S. Pederson Initiation of Base Excision Repair of Oxidative Lesions in Nucleosomes by the Human, Bifunctional DNA Glycosylase NTH1 Mol. Cell. Biol., December 15, 2007; 27(24): 8442 - 8453. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, R. Prasad, W. A. Beard, P. S. Kedar, E. W. Hou, D. D. Shock, and S. H. Wilson Coordination of Steps in Single-nucleotide Base Excision Repair Mediated by Apurinic/Apyrimidinic Endonuclease 1 and DNA Polymerase beta J. Biol. Chem., May 4, 2007; 282(18): 13532 - 13541. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Rose, K. C. Reeves, R. I. Likhotvorik, and D. G. Hoyt Base Excision Repair Proteins Are Required for Integrin-Mediated Suppression of Bleomycin-Induced DNA Breakage in Murine Lung Endothelial Cells J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 318 - 326. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Y. Chang, R. Komaki, R. Sasaki, Z. Liao, C. W. Stevens, C. Lu, F. V. Fossella, P. K. Allen, J. D. Cox, M. R. Spitz, et al. High Mutagen Sensitivity in Peripheral Blood Lymphocytes Predicts Poor Overall and Disease-Specific Survival in Patients with Stage III Non-Small Cell Lung Cancer Treated with Radiotherapy and Chemotherapy Clin. Cancer Res., April 15, 2005; 11(8): 2894 - 2898. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Luna, V. Rolseth, G. A. Hildrestrand, M. Otterlei, F. Dantzer, M. Bjoras, and E. Seeberg Dynamic relocalization of hOGG1 during the cell cycle is disrupted in cells harbouring the hOGG1-Cys326 polymorphic variant Nucleic Acids Res., March 30, 2005; 33(6): 1813 - 1824. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liu, W. A. Beard, D. D. Shock, R. Prasad, E. W. Hou, and S. H. Wilson DNA Polymerase {beta} and Flap Endonuclease 1 Enzymatic Specificities Sustain DNA Synthesis for Long Patch Base Excision Repair J. Biol. Chem., February 4, 2005; 280(5): 3665 - 3674. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pascucci, M. T. Russo, M. Crescenzi, M. Bignami, and E. Dogliotti The accumulation of MMS-induced single strand breaks in G1 phase is recombinogenic in DNA polymerase {beta} defective mammalian cells Nucleic Acids Res., January 12, 2005; 33(1): 280 - 288. [Abstract] [Full Text] [PDF]
|
|