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Methylcytosine and mutation
Genome Biologyvolume 3, Article number: spotlight-20020722-01 (2002)
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.
Role of MED1 (MBD4) Gene in DNA repair and human cancer
Multiple intestinal neoplasia caused by a mutation in the murine homolog of the APC gene.