CHEMISTRY AND BIOLOGY OF DNA METHYLTRANSFERASES

Recognition of a specific DNA sequence by a protein is probably the be st example of macromolecular interactions leading to various events. I t is a prerequisite to understanding the basis of protein-DNA interact ions to obtain a better insight into fundamental processes such as tra nscription, replication, repair, and recombination. DNA methyltransfer ases with varying sequence specificities provide an excellent model sy stem for understanding the molecular mechanism of specific DNA recogni tion. Sequence comparison of cloned genes, along with mutational analy ses and recent crystallographic studies, have clearly defined the func tions of various conserved motifs. These enzymes access their target b ase in an elegant manner by flipping it out of the DNA double helix. T he drastic protein-induced DNA distortion, first reported for HhaI DNA methyltransferase, appears to be a common mechanism employed by vario us proteins that need to act on bases. A remarkable feature of the cat alytic mechanism of DNA (cytosine-5) methyltransferases is the ability of these enzymes to induce deamination of the target cytosine in the absence of S-adenosyl-L-methionine or its analogs. The enzyme-catalyze d deamination reaction is postulated to be the major cause of mutation al hotspots at CpG islands responsible for various human genetic disor ders. Methylation of adenine residues in Escherichia coli is known to regulate various processes such as transcription, replication, repair, recombination, transposition, and phage packaging.