期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2005
卷号：102
期号：40
页码：14350-14355
DOI：10.1073/pnas.0505166102
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Thirty percent of the 189 tumors studied to date express DNA polymerase {beta} variants. One of these variants was identified in a prostate carcinoma and is altered from isoleucine to methionine at position 260, within the hydrophobic hinge region of the protein. Another variant was identified in a colon carcinoma and is altered at position 289 from lysine to methionine, within helix N of the protein. We have shown that the types of mutations induced by these cancer-associated variants are different from those induced by the wild-type enzyme. In this study, we show that expression of the I260M and K289M cancer-associated variants in mouse C127 cells results in a transformed phenotype in the great majority of cell clones tested, as assessed by focus formation and anchorage-independent growth. Strikingly, cellular transformation occurs after a variable number of passages in culture but, once established, does not require continuous expression of the polymerase {beta} variant proteins, implying that it has a mutational basis. Because DNA polymerase {beta} functions in base excision repair, our results suggest that mutations that arise during this process can lead to the onset or progression of cancer.
关键词：base excision repair ; DNA repair ; mutagenesis
