Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis.

Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Research Abstract Details 

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Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Abstract Text:

Laurie H Sanders,Andrea Rockel,Haiping Lu,Daniel J Wozniak,Mark D Sutton,

Pseudomonas aeruginosa is a human opportunistic pathogen that chronically infects the lungs of cystic fibrosis patients and is the leading cause of morbidity and mortality of people afflicted with this disease. A striking correlation between mutagenesis and the persistence of P. aeruginosa has been reported. In other well-studied organisms, error-prone replication by Y family DNA polymerases contributes significantly to mutagenesis. Based on an analysis of the PAO1 genome sequence, P. aeruginosa contains a single Y family DNA polymerase encoded by the dinB gene. As part of an effort to understand the mechanisms of mutagenesis in P. aeruginosa, we have cloned the dinB gene of P. aeruginosa and utilized a combination of genetic and biochemical approaches to characterize the activity and regulation of the P. aeruginosa DinB protein (DinB(Pa)). Our results indicate that DinB(Pa) is a distributive DNA polymerase that lacks intrinsic proofreading activity in vitro. Modest overexpression of DinB(Pa) from a plasmid conferred a mutator phenotype in both Escherichia coli and P. aeruginosa. An examination of this mutator phenotype indicated that DinB(Pa) has a propensity to promote C-->A transversions and -1 frameshift mutations within poly(dGMP) and poly(dAMP) runs. The characterization of lexA+ and DeltalexA::aacC1 P. aeruginosa strains, together with in vitro DNA binding assays utilizing cell extracts or purified P. aeruginosa LexA protein (LexA(Pa)), indicated that the transcription of the dinB gene is regulated as part of an SOS-like response. The deletion of the dinB(Pa) gene sensitized P. aeruginosa to nitrofurazone and 4-nitroquinoline-1-oxide, consistent with a role for DinB(Pa) in translesion DNA synthesis over N2-dG adducts. Finally, P. aeruginosa exhibited a UV-inducible mutator phenotype that was independent of dinB(Pa) function and instead required polA and polC, which encode DNA polymerase I and the second DNA polymerase III enzyme, respectively. Possible roles of the P. aeruginosa dinB, polA, and polC gene products in mutagenesis are discussed.

Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Publishing Authors By Initials

LH Sanders,A Rockel,H Lu,DJ Wozniak,MD Sutton,

For similar enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases: endopeptidases: serine endopeptidases research abstracts see: enzymes and coenzymes: enzymes: hydrolases: peptide hydrolases: endopeptidases: serine endopeptidases research

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Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of bacteriology

VOLUME: 188

Page Numbers: 8573-85

Journal Abbreviation: J. Bacteriol.

ISSN: 0021-9193

DAY: 13

MONTH: 10

YEAR: 2006

Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2985120

Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Keywords Mesh Terms:

KEYWORDS: Serine Endopeptidases

MESH TERMS: metabolism

Chemical & Substance for Abstract: Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis. Information

Substance Name: Serine Endopeptidases

Registry Number: EC 3.4.21.-

Grant and Affiliation Information for Role of Pseudomonas aeruginosa dinB-encoded DNA polymerase IV in mutagenesis.

AFFILIATION: Department of Biochemistry, School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 3435 Main Street, 140 Farber Hall, Buffalo, NY 14214, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL58334

ACRONYM: HL

MEDLINETA: J Bacteriol

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