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National Institute of Environmental Health Sciences

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Publication Detail

Title: A role for Pms2 in the prevention of tandem CC --> TT substitutions induced by ultraviolet radiation and oxidative stress.

Authors: Shin-Darlak, Chi Y; Skinner, Amy M; Turker, Mitchell S

Published In DNA Repair (Amst), (2005 Jan 2)

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 --> 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.

PubMed ID: 15533837 Exiting the NIEHS site

MeSH Terms: Adenine Phosphoribosyltransferase/genetics*; Adenosine Triphosphatases/genetics*; Animals; DNA Damage/genetics*; DNA Repair Enzymes/genetics*; DNA Repair*; DNA-Binding Proteins/genetics*; Hydrogen Peroxide/toxicity; Metals/toxicity; Mice; Mismatch Repair Endonuclease PMS2; Mutation/genetics; Oxidative Stress/genetics; Sequence Analysis, DNA; Tumor Cells, Cultured; Ultraviolet Rays

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