Figure 1. The schematic diagram of the different structural domains of DNMT1 and their functions. The N-terminal domain contains (1) a charge-rich DMAP domain which helps in interaction with the transcriptional repressor DMAP1 as well as controls the stability and binding of DNMT1 to DNA at CpG sites, (2) a PBD domain (Proliferating Cell Nuclear Antigen (PCNA) Binding Domain), which mediates the interaction of DNMT1 with PCNA and targets DNMT1 to the replication foci, (3) at least three independent functional NLS (Nuclear Localization Signal) sequences, (4) a RFTS [Replication Foci Targeting Sequence,also called TS (Targeting Sequence)] domain that targets the DNMT1 to replication foci and also mediates dimerization of DNMT1, (5) a zinc domain, also called as CXXC domain which is necessary for the catalytic activity of the enzyme and (6) a PBHD domain (Polybromo Homology Domain) containing two adjacent BAH sequence [BAH1 and BAH2 (Bromo-adjacent homology 1 and 2)]. The PBHD domain has been proposed to act as a protein–protein interaction module specialized in gene silencing. The C-terminal catalytic domain of DNMT1 contains ten characteristic sequence motifs (i.e., conserved motifs I–X), and the spacing sequences between VIII and IX motif is referred to as TRD. The coordination between N-terminal and C-terminal domains is essential for efficient catalytic activity as well as for its interactions with other protein regulators.