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Mechanistic details of the DNA recognition by the Dnmt1 DNA methyltransferase
Author(s) -
Bashtrykov Pavel,
Ragozin Sergey,
Jeltsch Albert
Publication year - 2012
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2012.05.026
Subject(s) - dna , dnmt1 , base pair , dna methyltransferase , cpg site , base (topology) , endonuclease , chemistry , biology , genetics , methyltransferase , dna methylation , gene , methylation , gene expression , mathematical analysis , mathematics
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.