Diversity of DNA methyltransferases that recognize asymmetric target sequences

Abstract

DNA methyltransferases (MTases) are a group of enzymes that catalyze the methyl group transfer from S-adenosyl-L-methionine in a sequence-specific manner. Orthodox Type II DNA MTases usually recognize palindromic DNA sequences and add a methyl group to the target base (either adenine or cytosine) on both strands. However, there are a number of MTases that recognize asymmetric target sequences and differ in their subunit organization. In a bacterial cell, after each round of replication, the substrate for any MTase is hemimethylated DNA, and it therefore needs only a single methylation event to restore the fully methylated state. This is in consistent with the fact that most of the DNA MTases studied exist as monomers in solution. Multiple lines of evidence suggest that some DNA MTases function as dimers. Further, functional analysis of many restriction-modification systems showed the presence of more than one or fused MTase genes. It was proposed that presence of two MTases responsible for the recognition and methylation of asymmetric sequences would protect the nascent strands generated during DNA replication from cognate restriction endonuclease. In this review, MTases recognizing asymmetric sequences have been grouped into different subgroups based on their unique properties. Detailed characterization of these unusual MTases would help in better understanding of their specific biological roles and mechanisms of action. The rapid progress made by the genome sequencing of bacteria and archaea may accelerate the identification and study of species- and strain-specific MTases of host-adapted bacteria and their roles in pathogenic mechanisms.

Keywords::

• Asymmetric MTases
• base flipping
• DNA MTases
• DNA–protein interactions
• oligomeric MTases
• R-M system
• sinefungin
• S-adenosyl-L- methionine

Acknowledgements

Work from our laboratory has been supported by grants from the DST, CSIR, DBT, and DAE, Government of India. UKM acknowledges CSIR for a senior research fellowship. We thank Ruchika Sharma, Arun Banerjee and Ritesh Kumar for carefully reading the manuscript and Shivakumar for helping us with the figures. DNR acknowledges J.C. Bose Fellowship from DST.

Editor: Michael M. Cox