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Molecular Enzymology of Mammalian DNA Methyltransferases

  • Chapter
Book cover DNA Methylation: Basic Mechanisms

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 301))

Abstract

DNA methylation is an essential modification of DNA in mammals that is involved in gene regulation, development, genome defence and disease. In mammals 3 families of DNA methyltransferases (MTases) comprising (so far) 4 members have been found: Dnmt1, Dnmt2, Dnmt3A and Dnmt3B. In addition, Dnmt3L has been identified as a stimulator of the Dnmt3A and Dnmt3B enzymes. In this review the enzymology of the mammalian DNA MTases is described, starting with a depiction of the catalytic mechanism that involves covalent catalysis and base flipping. Subsequently, important mechanistic features of the mammalian enzyme are discussed including the specificity of Dnmt1 for hemimethylated target sites, the target sequence specificity of Dnmt3A, Dnmt3B and Dnmt2 and the flanking sequence preferences of Dnmt3A and Dnmt3B. In addition, the processivity of the methylation reaction by Dnmt1, Dnmt3A and Dnmt3B is reviewed. Finally, the control of the catalytic activity of mammalian MTases is described that includes the regulation of the activity ofDnmt1 by its N-terminal domain and the interaction of Dnmt3A and Dnmt3B with Dnmt3L. The allosteric activation of Dnmt1 for methylation at unmodified sites is described. Wherever possible, correlations between the biochemical properties of the enzymes and their physiological functions in the cell are indicated.

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  1. School of Engineering and Science, International University Bremen, Campus Ring 1, 28759, Bremen, Germany

    A. Jeltsch

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  1. Institut für Genetik, Universität zu Köln, Zülpicher Str. 47, 50674, Köln, Germany

    Walter Doerfler (Prof. Dr.) & Petra Böhm (Prof. Dr.) & 

  2. Institut für Klinische und Molekulare Virologie, Universität Erlangen, Schlossgarten 4, 91054, Erlangen, Germany

    Walter Doerfler (Prof. Dr.) (Prof. Dr.)

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Jeltsch, A. (2006). Molecular Enzymology of Mammalian DNA Methyltransferases. In: Doerfler, W., Böhm, P. (eds) DNA Methylation: Basic Mechanisms. Current Topics in Microbiology and Immunology, vol 301. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-31390-7_7

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