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

This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ramotar, D. Articles by Drobetsky, E. A. Search for Related Content PubMed PubMed Citation Articles by Ramotar, D. Articles by Drobetsky, E. A. Social Bookmarking                      What's this?

J Biol Chem, Vol. 273, Issue 34, 21489-21496, August 21, 1998

A Yeast Homologue of the Human Phosphotyrosyl Phosphatase Activator PTPA Is Implicated in Protection against Oxidative DNA Damage Induced by the Model Carcinogen 4-Nitroquinoline 1-Oxide

From the Hôpital Maisonneuve-Rosemont, Centre de Recherche, Université de Montréal, Montréal, Québec H1T 2M4, Canada

The model carcinogen 4-nitroquinoline 1-oxide (4-NQO) has historically been characterized as "UV-mimetic" with respect to its genotoxic properties. However, recent evidence indicates that 4-NQO, unlike 254-nm UV light, may exert significant cytotoxic and/or mutagenic potential via the generation of reactive oxygen species. To elucidate the response of eukaryotic cells to 4-NQO-induced oxidative stress, we isolated Saccharomyces cerevisiae mutants exhibiting hypersensitivity to the cytotoxic effects of this mutagen. One such mutant, EBY1, was cross-sensitive to the oxidative agents UVA and diamide while retaining parental sensitivities to 254-nm UV light, methyl methanesulfonate, and ionizing radiation. A complementing gene (designated yPTPA1), restoring full UVA and 4-NQO resistance to EBY1 and encoding a protein that shares 40% identity with the human phosphotyrosyl phosphatase activator hPTPA, has been isolated. Targeted deletion of yPTPA1 in wild type yeast engendered the identical pattern of mutagen hypersensitivity as that manifested by EBY1, in addition to a spontaneous mutator phenotype that was markedly enhanced upon exposure to either UVA or 4-NQO but not to 254-nm UV or methyl methanesulfonate. Moreover, the yptpa1 deletion mutant exhibited a marked deficiency in the recovery of high molecular weight DNA following 4-NQO exposure, revealing a defect at the level of DNA repair. These data (i) strongly support a role for active oxygen intermediates in determining the genotoxic outcome of 4-NQO exposure and (ii) suggest a novel mechanism in yeast involving yPtpa1p-mediated activation of a phosphatase that participates in the repair of oxidative DNA damage, implying that hPTPA may exert a similar function in humans.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				K. Strati, H. C. Pitot, and P. F. Lambert Identification of biomarkers that distinguish human papillomavirus (HPV)-positive versus HPV-negative head and neck cancers in a mouse model PNAS, September 19, 2006; 103(38): 14152 - 14157. [Abstract] [Full Text] [PDF]

				J. Douville, J. David, K. M. Lemieux, L. Gaudreau, and D. Ramotar The Saccharomyces cerevisiae Phosphatase Activator RRD1 Is Required to Modulate Gene Expression in Response to Rapamycin Exposure Genetics, February 1, 2006; 172(2): 1369 - 1372. [Abstract] [Full Text] [PDF]

				S. Kozmin, G. Slezak, A. Reynaud-Angelin, C. Elie, Y. de Rycke, S. Boiteux, and E. Sage UVA radiation is highly mutagenic in cells that are unable to repair 7,8-dihydro-8-oxoguanine in Saccharomyces cerevisiae PNAS, September 20, 2005; 102(38): 13538 - 13543. [Abstract] [Full Text] [PDF]

				K. Felix, A. Polack, W. Pretsch, S. H. Jackson, L. Feigenbaum, G.-W. Bornkamm, and S. Janz Moderate Hypermutability of a Transgenic lacZ Reporter Gene in Myc-Dependent Inflammation-Induced Plasma Cell Tumors in Mice Cancer Res., January 15, 2004; 64(2): 530 - 537. [Abstract] [Full Text] [PDF]

				X.-H. Tang, B. Knudsen, D. Bemis, S. Tickoo, and L. J. Gudas Oral Cavity and Esophageal Carcinogenesis Modeled in Carcinogen-Treated Mice Clin. Cancer Res., January 1, 2004; 10(1): 301 - 313. [Abstract] [Full Text] [PDF]

				D. A. Mitchell and G. F. Sprague Jr. The Phosphotyrosyl Phosphatase Activator, Ncs1p (Rrd1p), Functions with Cla4p To Regulate the G2/M Transition in Saccharomyces cerevisiae Mol. Cell. Biol., January 15, 2001; 21(2): 488 - 500. [Abstract] [Full Text]

				J. Scheller, A. Schürer, C. Rudolph, S. Hettwer, and W. Kramer MPH1, A Yeast Gene Encoding a DEAH Protein, Plays a Role in Protection of the Genome From Spontaneous and Chemically Induced Damage Genetics, July 1, 2000; 155(3): 1069 - 1081. [Abstract] [Full Text]

				V. Janssens, C. Van Hoof, I. De Baere, W. Merlevede, and J. Goris The Phosphotyrosyl Phosphatase Activator Gene Is a Novel p53 Target Gene J. Biol. Chem., June 30, 2000; 275(27): 20488 - 20495. [Abstract] [Full Text] [PDF]