JBC INTERFERin siRNA transfection reagent

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.C100577200 on January 22, 2002

J. Biol. Chem., Vol. 277, Issue 10, 7637-7640, March 8, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/10/7637    most recent
C100577200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by DeMott, M. S.
Right arrow Articles by Demple, B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by DeMott, M. S.
Right arrow Articles by Demple, B.

ACCELERATED PUBLICATION
Covalent Trapping of Human DNA Polymerase beta  by the Oxidative DNA Lesion 2-Deoxyribonolactone*

Michael S. DeMottDagger §, Ergin BeyretDagger , Donny WongDagger , Brian C. Bales||, Jae-Taeg Hwang||, Marc M. Greenberg||, and Bruce DempleDagger **

From the Dagger  Department of Cancer Cell Biology, Harvard School of Public Health, Boston, Massachusetts 02115 and the || Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523

Oxidized abasic residues in DNA constitute a major class of radiation and oxidative damage. Free radical attack on the nucleotidyl C-1' carbon yields 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 beta  is impaired at dL compared with unmodified abasic sites. This inhibition is accompanied by accumulation of a protein-DNA cross-link not observed in reactions of polymerase beta  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 C-1 aldehyde during excision of an unmodified abasic site. In the case of a dL residue, attack on the lactone C-1 by lysine 72 proceeds more slowly and evidently produces an amide linkage, which resists further processing. Consequently dL residues may not be readily repaired by "short-patch" base excision repair but instead function as suicide substrates in the formation of protein-DNA cross-links that may require alternative modes of repair.

* This work was supported by National Institutes of Health Grants CA71993 (to B. D. and M. M. G.), GM40000 (to B. D.), and GM54996 and CA74954 (to M. M. G.). General support was through the Kresge Center for Environmental Health Sciences of Harvard School of Public Health.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ Supported by Training Grant T32-CA09078 from the NCI, National Institutes of Health.

Supported in part by Training Grant T32-ES07155 from the NIEHS, National Institutes of Health.

** To whom correspondence should be addressed. Tel.: 617-432-3462; Fax: 617-432-0377; E-mail: bdemple@hsph.harvard.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 Clin. Cancer Res.Home page
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]

Home page
 Nucleic Acids ResHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 Nucleic Acids ResHome page
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]

Home page
 J. Biol. Chem.Home page
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]

Home page
 J. Biol. Chem.Home page
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 TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.