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- W63457237 abstract "In Escherichia coli and human cells, many sites of cytosine methylation in DNA are hot spots for C to T mutations. It is generally believed that T.G mismatches created by the hydrolytic deamination of 5-methylcytosines (5meC) are intermediates in the mutagenic pathway. A number of hypotheses have been proposed regarding the source of the mispaired thymine and how the cells deal with the mispairs. We have constructed a genetic reversion assay that utilizes a gene on a mini-F to compare the frequency of occurrence of C to T mutations in different genetic backgrounds in exponentially growing E. coli. The results identify at least two causes for the hot spot at a 5meC: (1) the higher rate of deamination of 5meC compared to C generates more T.G than uracil.G (U.G) mismatches, and (2) inefficient repair of T.G mismatches by the very short-patch (VSP) repair system compared to the repair of U. G mismatches by the uracil-DNA glycosylase (Ung). This combination of increased DNA damage when the cytosines are methylated coupled with the relative inefficiency in the post-replicative repair of T.G mismatches can be quantitatively modeled to explain the occurrence of the hot spot at 5meC. This model has implications for mutational hot and cold spots in all organisms." @default.
- W63457237 created "2016-06-24" @default.
- W63457237 creator A5074923093 @default.
- W63457237 creator A5075917155 @default.
- W63457237 date "1999-07-01" @default.
- W63457237 modified "2023-10-17" @default.
- W63457237 title "Principal causes of hot spots for cytosine to thymine mutations at sites of cytosine methylation in growing cells" @default.
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- W63457237 doi "https://doi.org/10.1016/s1383-5742(99)00065-4" @default.
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