| First Author | Shin-Darlak CY | Year | 2005 |
| Journal | DNA Repair (Amst) | Volume | 4 |
| Issue | 1 | Pages | 51-7 |
| PubMed ID | 15533837 | Mgi Jnum | J:94446 |
| Mgi Id | MGI:3512822 | Doi | 10.1016/j.dnarep.2004.08.006 |
| Citation | Shin-Darlak CY, et al. (2005) A role for Pms2 in the prevention of tandem CC --> TT substitutions induced by ultraviolet radiation and oxidative stress. DNA Repair (Amst) 4(1):51-7 |
| abstractText | DNA mismatch repair (MMR) is important for preventing base-pair substitutions caused by spontaneous or damage-related DNA polymerase errors. We have used a reversion assay based on mouse Aprt to investigate the role of MMR in preventing ultraviolet radiation (UV) and oxidative stress induced tandem CC --> TT base pair substitutions in cultured mammalian cells. The reversion construct used for this assay can detect both C --> T and CC --> TT mutational events. Most spontaneous mutations in Pms2-deficient cells were single C --> T substitutions (88%), with the remainder being tandem CC --> TT substitutions (12%). The percentage of tandem CC --> TT substitutions rose to 64% and 94% for Pms2-deficient cells exposed to UV and a mixture of hydrogen peroxide and metals (Cu/Fe), respectively. Exposure to hydrogen peroxide alone or metals alone did not induce the tandem substitutions, nor did treatment of the cells with the alkylating agent ethylmethane sulfonate, which induces G --> A substitutions on the opposite strand. Tandem CC --> TT substitutions were also induced by UV irradiation and the hydrogen peroxide/metal mixture in Pms2-proficient cells, but at frequencies significantly lower than those observed in the Pms2-deficient cells. We conclude that mismatch repair plays an important role in preventing tandem CC --> TT substitutions induced by certain genotoxin exposures. |
