Over the past ten years, work in the field of DNA NMR has made it possible to record not only canonical Watson-Crick pairs in DNA, but also non-canonical pairs that exist several milliseconds. It turned out that almost all possible ways to connect nucleotides are realized under physiological conditions in ordinary DNA. Properties of non-canonical GC Base Pairs and their relation with mechanochemical cleavage of DNA are analyzed here. A hypothesis of the involvement of the Transient GC Wobble Base Pairs in the mechanisms of the mechanochemical cleavage of DNA and epigenetic mechanisms with participation of 5-methylcytosine is proposed. The hypothesis explains the increase in the frequency of the breaks of the sugar-phosphate backbone of DNA after cytosine, asymmetric character of these breaks, and an increase in the frequency of breaks in CpG after cytosine methylation . The epigenetic properties of 5-hydroxymethylcytosine, 5-formylcytosine, and N4-methylcytosine are also explained within our hypothesis. There is an idea that regulatory proteins do not recognize the methyl group on the cytosine, but a much larger distortion of the DNA structure caused by the GC Wobble pair. GC Wobble pair allows to explain the increased frequency of cytosine deamination, that is, the high frequency of mutations in regulatory sites.
mechanochemical cleavage of DNA, transient Base Pairs in DNA, Wobble Base Pair, tautomer, 5-methylcytosine, molecular basis of epigenetics
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