| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Papers In Press, published online ahead of print January 22, 2002
J. Biol. Chem, 10.1074/jbc.C100577200
Submitted on October 5, 2001
Revised on January 7, 2002
Accepted on January 18, 2002
Cancer Cell Biology, Harvard School of Public Health, Boston, MA 02115
Corresponding Author: bdemple{at}hsph.harvard.edu
Oxidized abasic residues in DNA constitute a major class of radiation and oxidative damage. Free radical attack on the nucleotidyl C1' carbon yield 2-deoxyribonolactone (dL) as a significant lesion. Although dL residues are efficiently incised by the main human abasic endonuclease enzyme Ape1, we show here that subsequent excision by human DNA polymerase 
is strongly inhibited compared to unmodified abasic sites. This inhibition is accompanied by accumulation of a protein-DNA cross-link not observed in reactions of polymerase with unmodified abasic sites, although a similar form can be trapped by reduction with sodium borohydride. The formation of the stably cross-linked species with dL depends on the polymerase lysine-72 residue, which forms a Schiff base with the C1-aldehyde during excision of an unmodified abasic site. In the case of a dL residue, attack on the lactone C1 by lysine-72 proceeds more slowly and evidently produces an amide linkage, which resists further processing. Consequently, dL residues appear not to be readily repaired by "short-patch" base excision repair but instead function as suicide substrates in the formation of a protein-DNA cross-link that may require alternative modes of repair.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Parr, A. J. Sanders, G. Davies, T. Martin, J. Lane, M. D. Mason, R. E. Mansel, and W. G. Jiang Matriptase-2 Inhibits Breast Tumor Growth and Invasion and Correlates with Favorable Prognosis for Breast Cancer Patients Clin. Cancer Res., June 15, 2007; 13(12): 3568 - 3576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. O. Blaisdell and S. S. Wallace Rapid determination of the active fraction of DNA repair glycosylases: a novel fluorescence assay for trapped intermediates Nucleic Acids Res., March 12, 2007; 35(5): 1601 - 1611. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. T. Reardon and A. Sancar Repair of DNA-polypeptide crosslinks by human excision nuclease. PNAS, March 14, 2006; 103(11): 4056 - 4061. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Sung, M. S. DeMott, and B. Demple Long-patch Base Excision DNA Repair of 2-Deoxyribonolactone Prevents the Formation of DNA-Protein Cross-links with DNA Polymerase {beta} J. Biol. Chem., November 25, 2005; 280(47): 39095 - 39103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Wong and B. Demple Modulation of the 5'-Deoxyribose-5-phosphate Lyase and DNA Synthesis Activities of Mammalian DNA Polymerase {beta} by Apurinic/Apyrimidinic Endonuclease 1 J. Biol. Chem., June 11, 2004; 279(24): 25268 - 25275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Faure, J.-F. Constant, P. Dumy, and M. Saparbaev 2'-Deoxyribonolactone lesion produces G->A transitions in Escherichia coli Nucleic Acids Res., May 24, 2004; 32(9): 2937 - 2946. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nakano, H. Terato, K. Asagoshi, A. Masaoka, M. Mukuta, Y. Ohyama, T. Suzuki, K. Makino, and H. Ide DNA-Protein Cross-link Formation Mediated by Oxanine: A NOVEL GENOTOXIC MECHANISM OF NITRIC OXIDE-INDUCED DNA DAMAGE J. Biol. Chem., June 27, 2003; 278(27): 25264 - 25272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Harrigan, P. L. Opresko, C. von Kobbe, P. S. Kedar, R. Prasad, S. H. Wilson, and V. A. Bohr The Werner Syndrome Protein Stimulates DNA Polymerase {beta} Strand Displacement Synthesis via Its Helicase Activity J. Biol. Chem., June 13, 2003; 278(25): 22686 - 22695. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |
