The Mbd4 DNA glycosylase protects mice from inflammation-driven colon cancer and tissue injury.

ABSTRACT: Much of the global cancer burden is associated with longstanding inflammation accompanied by release of DNA-damaging reactive oxygen and nitrogen species. Here, we report that the Mbd4 DNA glycosylase is protective in the azoxymethane/dextran sodium sulfate (AOM/DSS) mouse model of inflammation-driven colon cancer. Mbd4 excises T and U from T:G and U:G mismatches caused by deamination of 5-methylcytosine and cytosine. Since the rate of deamination is higher in inflamed tissues, we investigated the role of Mbd4 in inflammation-driven tumorigenesis. In the AOM/DSS assay, Mbd4-/- mice displayed more severe clinical symptoms, decreased survival, and a greater tumor burden than wild-type (WT) controls. The increased tumor burden in Mbd4-/- mice did not arise from impairment of AOM-induced apopt

SUBMITTER: Yu AM 

PROVIDER: S-EPMC5053750 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature