Erasing methylation marks on DNA by plant-specific DEMETER family DNA glycosylases

Abstract

Plants, being sessile and incapable of evading the continually fluctuating environment, display enormous plasticity in responding to constantly changing environmental challenges through assimilating changes in the genome (resulting in sequence polymorphism) and epigenome (resulting in gene expression alterations). DNA methylation is one of the reversible epigenetic modifications imparting a swift tunability to the genome through a complex interplay of methylation and demethylation processes. Plants have diligently repurposed the base excision repair machinery to actively erase methylation marks on DNA by evolving a specific family of HhH DNA glycosylases collectively called the DEMETER family. The DML family comprises four types of HhH DNA glycosylases: DEMETER, REPRESSOR OF SILENCING 1, and the paralogs DML2 and DML3 (DEMETER-LIKE proteins 2 and 3). The DML family enzymes are bifunctional glycosylases with a bipartite glycosylase domain and a C-terminal domain crucial for the catalytic activity. Removal of methylation proceeds through a classical mechanism of DNA bending and base flipping. DML family DNA glycosylases play roles in maintaining genome stability, plant development, and various biotic and abiotic stresses. This review aims to provide a comprehensive summary of the current understanding of the molecular mechanisms and biological functions of the DEMETER family DNA glycosylases in plants.