Enzymic removal of 5-methylcytosine from DNA by a human DNA-glycosylase

摘要: DNA 5-methylcytosine is a major factor in the silencing of mammalian genes; it involved gene expression, differentiation, embryogenesis and neoplastic transformation. A decrease content associated with activation specific genes. There much evidence indicating this to be an enzymic process, replacement by cytosine. We demonstrate here release 5-methylcytosines from human 5-methylcytosine-DNA glycosylase activity, which affords possible mechanism for such replacement. This activity generates promutagenic apyrimidinic sites, can related high frequency mutations found at loci. The recovery most released pyrimidines as thymines indicates subsequent deamination free deaminase activity. prevents recycling into replicative synthesis via 5-methyl-dCTP intermediate synthesized through pyrimidine salvage pathway. Taken together, these findings indicate mechanisms removal DNA, hypermutability exclusion during replication.