title: Multimerization of the dnmt3a DNA methyltransferase and its functional implications.
abstract: The Dnmt3a DNA cytosine-C5 methyltransferase has been recently shown to exhibit a complex oligomerization and multimerization potential, the structural basis and functional implications of which will be the subject of this contribution. The enzyme forms a linear heterotetramer with Dnmt3L, in which the interaction of Dnmt3a and 3L stimulates the catalytic activity of Dnmt3a. Isolated Dnmt3a forms protein filaments that bind to several DNA molecules oriented in parallel, which plays an essential role in the location of the enzyme to heterochromatin. Dnmt3L disrupts Dnmt3a protein filaments and leads to a redistribution of the enzyme in cells toward euchromatin. Finally, Dnmt3a complexes and Dnmt3a/3L heterotetramers cooperatively multimerize on DNA forming protein-DNA filaments. This leads to a preference of the enzyme for periodic methylation of DNA and supports its heterochromatic localization.
authors.affiliation: Institute of Biochemistry, Stuttgart University, Stuttgart, Germany.
authors.forename: Albert
authors.initials: A
authors.lastname: Jeltsch
authors.forename: Renata Z
authors.initials: RZ
authors.lastname: Jurkowska
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D055162:Biocatalysis; D004247:DNA / Q000378:metabolism; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D019175:DNA Methylation; D000090205:DNA Methyltransferase 3A; D006801:Humans; D008969:Molecular Sequence Data; D055503:Protein Multimerization
chemical_list: C000717967:DNMT3A protein, human; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; D000090205:DNA Methyltransferase 3A