This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Wang, M. Articles by You, M. Search for Related Content PubMed PubMed Citation Articles by Wang, M. Articles by You, M.

Pol Is a Candidate for the Mouse Pulmonary Adenoma Resistance 2 Locus, a Major Modifier of Chemically Induced Lung Neoplasia

¹ Department of Surgery and The Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri; ² Laboratory of Molecular Carcinogenesis and ³ Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina; and ⁴ Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan

In this study, we performed systematic candidate gene analyses of the Pulmonary adenoma resistance 2 locus. Differential gene expression in lung tissues and nucleotide polymorphisms in coding regions between A/J and BALB/cJ mice were examined using reverse transcription-PCR and direct sequencing. Although not all genes in the interval were analyzed at this moment due to the recent database updating, we have found that the Pol gene, encoding the DNA polymerase , contains 25 nucleotide polymorphisms in its coding region between A/J and BALB/cJ mice, resulting in a total of ten amino acid changes. Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors. Altered expression of POL protein and an amino acid-changing nucleotide polymorphism were observed in human lung cancer cells, suggesting a possible role in the development of lung cancer. Thus, our data support the Pol gene as a modifier of lung tumorigenesis by altering DNA polymerase activity.

This article has been cited by other articles:

				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]

				C. A. Dumstorf, A. B. Clark, Q. Lin, G. E. Kissling, T. Yuan, R. Kucherlapati, W. G. McGregor, and T. A. Kunkel Participation of mouse DNA polymerase {iota} in strand-biased mutagenic bypass of UV photoproducts and suppression of skin cancer PNAS, November 28, 2006; 103(48): 18083 - 18088. [Abstract] [Full Text] [PDF]

				T. Ohkumo, Y. Kondo, M. Yokoi, T. Tsukamoto, A. Yamada, T. Sugimoto, R. Kanao, Y. Higashi, H. Kondoh, M. Tatematsu, et al. UV-B Radiation Induces Epithelial Tumors in Mice Lacking DNA Polymerase {eta} and Mesenchymal Tumors in Mice Deficient for DNA Polymerase {iota} Mol. Cell. Biol., October 15, 2006; 26(20): 7696 - 7706. [Abstract] [Full Text] [PDF]

				T. S. Fenske, C. McMahon, D. Edwin, J. C. Jarvis, J. M. Cheverud, M. Minn, V. Mathews, M. A. Bogue, M. A. Province, H. L. McLeod, et al. Identification of candidate alkylator-induced cancer susceptibility genes by whole genome scanning in mice. Cancer Res., May 15, 2006; 66(10): 5029 - 5038. [Abstract] [Full Text] [PDF]

				J.-Y. Choi and F. P. Guengerich Kinetic Evidence for Inefficient and Error-prone Bypass across Bulky N2-Guanine DNA Adducts by Human DNA Polymerase {iota} J. Biol. Chem., May 5, 2006; 281(18): 12315 - 12324. [Abstract] [Full Text] [PDF]