Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10823706 | DNA Repair | 2005 | 7 Pages |
Abstract
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 â TT base pair substitutions in cultured mammalian cells. The reversion construct used for this assay can detect both C â T and CC â TT mutational events. Most spontaneous mutations in Pms2-deficient cells were single C â T substitutions (88%), with the remainder being tandem CC â TT substitutions (12%). The percentage of tandem CC â 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 â A substitutions on the opposite strand. Tandem CC â 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 â TT substitutions induced by certain genotoxin exposures.
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Authors
Chi Y. Shin-Darlak, Amy M. Skinner, Mitchell S. Turker,