DNA methyltransferases: Mechanistic models derived from kinetic analysis

• Published in: Critical reviews in biochemistry and molecular biology Vol. 47; no. 2; pp. 97 - 193
• Main Authors: Malygin, Ernst G., Hattman, Stanley
• Format: Journal Article
• Language: English
• Published: England Informa Healthcare 01.03.2012; Taylor & Francis
• Subjects: Adenine - metabolism; Animals; Base flipping; Base Sequence; Cytosine - metabolism; DNA Methylation; DNA Modification Methylases - genetics; DNA Modification Methylases - metabolism; Epigenesis, Genetic; hemi-methylation; Humans; Kinetics; Models, Molecular; Molecular Sequence Data; mutational analysis; pre-steady state; processivity; S-adenosyl-L-methionine; S-Adenosylmethionine - metabolism; single turnover; Substrate Specificity
• DOI: 10.3109/10409238.2011.620942
• ISSN: 1040-9238

The sequence-specific transfer of methyl groups from donor S-adenosyl-L-methionine (AdoMet) to certain positions of DNA-adenine or -cytosine residues by DNA methyltransferases (MTases) is a major form of epigenetic modification. It is virtually ubiquitous, except for some notable exceptions. Site-specific methylation can be regarded as a means to increase DNA information capacity and is involved in a large spectrum of biological processes. The importance of these functions necessitates a deeper understanding of the enzymatic mechanism(s) of DNA methylation. DNA MTases fall into one of two general classes; viz. amino-MTases and [C5-cytosine]-MTases. Amino-MTases, common in prokaryotes and lower eukaryotes, catalyze methylation of the exocyclic amino group of adenine ([N6-adenine]-MTase) or cytosine ([N4-cytosine]-MTase). In contrast, [C5-cytosine]-MTases methylate the cyclic carbon-5 atom of cytosine. Characteristics of DNA MTases are highly variable, differing in their affinity to their substrates or reaction products, their kinetic parameters, or other characteristics (order of substrate binding, rate limiting step in the overall reaction). It is not possible to present a unifying account of the published kinetic analyses of DNA methylation because different authors have used different substrate DNAs and/or reaction conditions. Nevertheless, it would be useful to describe those kinetic data and the mechanistic models that have been derived from them. Thus, this review considers in turn studies carried out with the most consistently and extensively investigated [N6-adenine]-, [N4-cytosine]- and [C5-cytosine]-DNA MTases.