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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Kunkel, Thomas A. Clark, Alan B. Yuan, Tao Dumstorf, Chad A. Kucherlapati, Raju Mcgregor, W. Glenn Lin, Qingcong Kissling, Grace E. |
| Description | Author Affiliation: Dumstorf CA ( Department of Pharmacology and Toxicology and James Graham Brown Cancer Center, University of Louisville, Louisville, KY 40202-1786, USA.); |
| Abstract | DNA polymerase iota (pol iota) is a conserved Y family enzyme that is implicated in translesion DNA synthesis (TLS) but whose cellular functions remain uncertain. To test the hypothesis that pol iota performs TLS in cells, we compared UV-induced mutagenesis in primary fibroblasts derived from wild-type mice to mice lacking functional pol eta, pol iota, or both. A deficiency in mouse DNA polymerase eta (pol eta) enhanced UV-induced Hprt mutant frequencies. This enhanced UV-induced mutagenesis and UV-induced mutagenesis in wild-type cells were strongly diminished in cells deficient in pol iota, indicating that pol iota participates in the bypass of UV photoproducts in cells. Moreover, a clear strand bias among UV-induced base substitutions was observed in wild-type cells that was diminished in pol eta- and pol iota-deficient mouse cells and abolished in cells deficient in both enzymes. These data suggest that these enzymes bypass UV photoproducts in an asymmetric manner. To determine whether pol iota status affects cancer susceptibility, we compared the UV-induced skin cancer susceptibility of wild-type mice to mice lacking functional pol eta, pol iota, or both. Although pol iota deficiency alone had no effect, UV-induced skin tumors in pol eta-deficient mice developed 4 weeks earlier in mice concomitantly deficient in pol iota. Collectively, these data reveal functions for pol iota in bypassing UV photoproducts and in delaying the onset of UV-induced skin cancer. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Damage DNA-Directed DNA Polymerase Metabolism Mutagenesis Genetics Skin Neoplasms Enzymology Pathology Ultraviolet Rays Animals Cell Survival Radiation Effects Cells, Cultured Deficiency Fibroblasts Mice Mice, Knockout Sensitivity And Specificity Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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