Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferase.
A recently solved Dnmt1-DNA crystal structure revealed several enzyme-DNA contacts and large structural rearrangements of the DNA at the target site, including the flipping of the non-target strand base of the base pair flanking the CpG site and formation of a non-canonical base pair between the non-target strand Gua and the flanking base pair. Here, we show that the contacts of the enzyme to the target base and the Gua:5mC base pair that are observed in the structure are very important for catalytic activity. The contacts to the non-target strand Gua are not important since its exchange by Ade stimulated activity. Except target base flipping, we could not find evidence that the DNA rearrangements have a functional role.
Institute of Biochemistry, Faculty of Chemistry, University Stuttgart, Germany.
Pavel
P
Bashtrykov
Sergey
S
Ragozin
Albert
A
Jeltsch
D020029:Base Pairing; D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000378:metabolism; D015321:Gene Rearrangement; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary
D004247:DNA; D000076123:DNA (Cytosine-5-)-Methyltransferase 1; D004248:DNA (Cytosine-5-)-Methyltransferases; D015226:Dinucleoside Phosphates; C015772:CpG dinucleotide