A Comprehensive Review of Structural Insights into DNA Methylation Maintenance

Abstract

DNA methylation is faithfully inherited during cell division, playing a crucial role in maintaining cellular identity. The process of DNA methylation maintenance relies on DNA methyltransferase DNMT1 and the ubiquitin E3 ligase UHRF1. UHRF1 facilitates the ubiquitination of both the replication factor PAF15 and histone H3, with each ubiquitin signal regulating replication-coupled and uncoupled DNA methylation maintenance, respectively. Over the past decades, advances in structural biology have significantly deepened our understanding of the molecular mechanisms governing DNA methylation maintenance. In particular, the emergence of cryo-electron microscopy (cryo-EM)—often referred to as the “Resolution Revolution”—has transformed many areas of biology, including epigenetics and chromatin biology. This review focuses on the structural mechanisms of DNA methylation maintenance, as revealed by the three-dimensional structures of key biomolecular complexes and discusses the potential development of inhibitors targeting DNA methylation maintenance factors based on structural insights.