HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 282, Issue 17, 12741-12748, April 27, 2007

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 282/17/12741    most recent M700575200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Neeley, W. L. Articles by Essigmann, J. M. Search for Related Content PubMed PubMed Citation Articles by Neeley, W. L. Articles by Essigmann, J. M. Social Bookmarking                      What's this?

DNA Polymerase V Allows Bypass of Toxic Guanine Oxidation Products in Vivo^*

William L. Neeley, Sarah Delaney¹, Yuriy O. Alekseyev, Daniel F. Jarosz, James C. Delaney, Graham C. Walker^¶, and John M. Essigmann²

From the Department of Chemistry, Biological Engineering Division, and ^¶Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139

Reactive oxygen and nitrogen radicals produced during metabolic processes, such as respiration and inflammation, combine with DNA to form many lesions primarily at guanine sites. Understanding the roles of the polymerases responsible for the processing of these products to mutations could illuminate molecular mechanisms that correlate oxidative stress with cancer. Using M13 viral genomes engineered to contain single DNA lesions and Escherichia coli strains with specific polymerase (pol) knockouts, we show that pol V is required for efficient bypass of structurally diverse, highly mutagenic guanine oxidation products in vivo. We also find that pol IV participates in the bypass of two spiroiminodihydantoin lesions. Furthermore, we report that one lesion, 5-guanidino-4-nitroimidazole, is a substrate for multiple SOS polymerases, whereby pol II is necessary for error-free replication and pol V for error-prone replication past this lesion. The results spotlight a major role for pol V and minor roles for pol II and pol IV in the mechanism of guanine oxidation mutagenesis.

Received for publication, January 19, 2007 , and in revised form, February 20, 2007.

^* This work was supported in part by National Institutes of Health Grants CA26731, CA080024, and CA21615, NIEHS Center Grant P30ES02109 from the National Institutes of Health, and National Science Foundation Grants DBI-9729592 and CHE-9808061. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental text, Figs. S1–S11, and supplemental Refs. 1–12.

¹ Damon Runyon Fellow supported by the Damon Runyon Cancer Research Foundation Grant DRG1848-04.

² To whom correspondence should be addressed. Tel.: 617-253-6227; Fax: 617-253-5445; E-mail: jessig{at}mit.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				H. Hong, H. Cao, and Y. Wang Formation and genotoxicity of a guanine cytosine intrastrand cross-link lesion in vivo Nucleic Acids Res., December 18, 2007; 35(21): 7118 - 7127. [Abstract] [Full Text] [PDF]

				W. Yang and R. Woodgate What a difference a decade makes: Insights into translesion DNA synthesis PNAS, October 2, 2007; 104(40): 15591 - 15598. [Abstract] [Full Text] [PDF]

				M. d. Vega and M. Salas A highly conserved Tyrosine residue of family B DNA polymerases contributes to dictate translesion synthesis past 8-oxo-7,8-dihydro-2'-deoxyguanosine Nucleic Acids Res., August 1, 2007; (2007) gkm545v2. [Abstract] [Full Text] [PDF]

				S. Saumaa, A. Tover, M. Tark, R. Tegova, and M. Kivisaar Oxidative DNA Damage Defense Systems in Avoidance of Stationary-Phase Mutagenesis in Pseudomonas putida J. Bacteriol., August 1, 2007; 189(15): 5504 - 5514. [Abstract] [Full Text] [PDF]