Specific in vitro binding of p53 to the promoter region of the human mismatch repair gene hMSH2.

MSH2 is one of the genes involved in DNA-mismatch repair. Mutations in the coding region of the human gene (hMSH2) have been shown to be directly involved in microsatellite instability in hereditary nonpolyposis colorectal tumors. Examination of the promoter region of hMHS2 revealed a site with homology to the p53 consensus binding sequence. Using gel mobility shift experiments we were able to show that purified p53 has at least in vitro the potential to specifically bind the hMSH2-p53 motif. This binding activity was even stronger than the binding activity measured with the p53-consensus site. These data identify the hMSH2 gene as a possible novel p53-regulated target gene and indicate a direct involvement of p53 in repair mechanisms via DNA binding of a mismatch repair gene.