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• W822073298 endingPage "111" @default.
• W822073298 startingPage "65" @default.
• W822073298 abstract "This chapter describes the enzymological boundaries of the phenomenon of human deoxyribonucleic acid (DNA) methylation, set by the specificity and mechanism of action of the human DNA methyltransferase(s). The formation of a tight, and presumably covalent, complex, between DNA, containing 5-azacytosine and DNA (cytosine-5) methyltransferases, from both bacterial and human sources, is consistent, with a mechanism of action of the enzymes, involving the production of a covalent dihydrocytosine intermediate in DNA. The phenomenon of concerted modification of interspersed repeated sequences defines the fundamental requirements for the establishment of methylation patterns. Cis-acting sequence elements must be coupled, with trans-acting factors that modulate methylation, at multiple loci in identical sequences. The activation of the human enzyme, by alterations in stacking energy, at the C-G sequence predicts the existence of chromosome structures or site-specific DNA-binding proteins that will activate site-specific de novo methylation, by presenting unstacked or protonated cytosines in the C-G site to the DNA methyltransferase. According to current theory, the displaced cytosine is a transition state analog for which the methyltransferase would have a high affinity. An additional acceleration of the reaction, by structures, containing a C–C mispair, suggests that nucleophilic attack at C-6 is facilitated, by protonation of N-3 in the mispair, since one of the cytosines in this mispair is both protonated and displaced into the major groove. Ab initio calculations of the charge distribution on the protonated cytosine ring support this notion, since the net positive charge at C-6 is, in fact, increased by protonation at N-3." @default.
• W822073298 created "2016-06-24" @default.
• W822073298 creator A5067251348 @default.
• W822073298 date "1994-01-01" @default.
• W822073298 modified "2023-09-27" @default.
• W822073298 title "Biological Implications of the Mechanism of Action of Human DNA (Cytosine-5)methyltransferase" @default.
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