Expression of DNA polymerase {beta} cancer-associated variants in mouse cells results in cellular transformation
| Autor: | Shibani Dalal, Char-Chang Lai, Daniel DiMaio, Joann B. Sweasy, Ka-Wai Sun, Daniela Starcevic, Tieming Lang |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
DNA Repair
DNA polymerase DNA repair Blotting Western Genetic Vectors DNA polymerase beta medicine.disease_cause Cell Line chemistry.chemical_compound Mice medicine Animals DNA Polymerase beta Mutation Multidisciplinary Methionine biology Base excision repair Biological Sciences Molecular biology Phenotype Cell Transformation Neoplastic Retroviridae chemistry Cell culture biology.protein |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 102(40) |
| ISSN: | 0027-8424 |
| Popis: | Thirty percent of the 189 tumors studied to date express DNA polymerase β 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 β variant proteins, implying that it has a mutational basis. Because DNA polymerase β functions in base excision repair, our results suggest that mutations that arise during this process can lead to the onset or progression of cancer. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|