The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA.

Abstract

The modified base, 5-methylcytosine, constitutes approximately 1% of human DNA, but sites containing 5-methylcytosine account for at least 30% of all germline and somatic point mutations. A genetic assay with a sensitivity of 1 in 10(7), based on reversion to neomycin resistance of a mutant pSV2-neo plasmid, was utilized to determine and compare the deamination rates of 5-methylcytosine and cytosine in double-stranded DNA for the first time. The rate constants for spontaneous hydrolytic deamination of 5-methylcytosine and cytosine in double-stranded DNA at 37 degrees C were 5.8 x 10(-13) s-1 and 2.6 x 10(-13) s-1, respectively. These rates are more than sufficient to explain the observed frequency of mutation at sites containing 5-methylcytosine and emphasize the importance of hydrolytic deamination as a major source of human mutations.

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@article{Shen1994TheRO, title={The rate of hydrolytic deamination of 5-methylcytosine in double-stranded DNA.}, author={Jiang Cheng Shen and William M. Rideout and Peter A. Jones}, journal={Nucleic acids research}, year={1994}, volume={22 6}, pages={972-6} }