Molecular enzymology of DNA cytosine-5 methylation. DNAメチル化の分子酵素学

ゲノムのメチル化は、シーケンスだけによらない遺伝（エピジェネティックス）の機構の一つとして注目されています。クリマサウカス博士は、DNAメチル化が塩基をDNAへリックスから飛び出させることを発見し、反応の詳細を解析しています。

Postreplicative methylation of cytosine residues in DNA plays important physiological roles in both prokaryotes and eukaryotes. DNA methyltransferases (MTases) recognice specific sequenses and flip a target base out of the DNA helix for methylation. Our goal is to understand how these unique enzymes work. Using the cytosine-5 MTase HhaI as a model system, we study the mechanisms of base flipping and catalysis by applying methods of mutagenesis, NMR and fluorescence spectroscopy, affinity cross-linking and kinetic analysis. A combination of domain swaps and X-ray crystallography serves to elucidate the molecular basis for the wide diversity of sequence specificities of these enzymes.