WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts.

Recent studies in yeast have found that processing of DNA double-strand breaks (DSB) for recombination repair involves Sgs1 helicase. Human cells have five Sgs1 homologues with unknown selectivity and significance for repair of different DSB types. Here we examined the importance of WRN helicase in repair of G(2)-specific DSB caused by abnormal mismatch repair (MMR) of ternary Cr-DNA adducts.

Rapid DNA double-strand breaks resulting from processing of Cr-DNA cross-links by both MutS dimers.

Mismatch repair (MMR) strongly enhances cyto- and genotoxicity of several chemotherapeutic agents and environmental carcinogens. DNA double-strand breaks (DSB) formed after two replication cycles play a major role in MMR-dependent cell death by DNA alkylating drugs. Here, we examined DNA damage detection and the mechanisms of the unusually rapid induction of DSB by MMR proteins in response to carcinogenic chromium(VI).