Methylcytosine and mutation

MBD4 is a methyl-CpG-binding protein with thymine-DNA-glycolase activity that can remove T bases from T-G mismatches within a CpG context. In the July 19 Science, Millar et al. describe analysis of mice lacking the Mbd4 gene (Science 2002, 297:403-405). They generated Mbd4-/- knockout mice and bred them with the 'Big Blue' reporter strain to measure mutation frequency. They found that the knockout mice had a three-fold higher frequency of C to T transitions at CpG sites. Then Millar et al. tested the effect of Mbd4 mutation on cancer susceptibility. They crossed Mbd4-/- knockout mice with animals carrying the Min allele of the adenomatous polyposis coli gene (ApcMin). They observed increased tumor formation in the colon and C to T mutations in the Apc gene. These results provide further evidence for the role of MBD4 in tumor suppression.