Recognition of Methylcytosine

Recognition of methylated status of CpG

The methytransferase itself exhibit capability of evalutating the methylation status of substrate.

The hemimethylated DNA duplex is embedded in the catalytic cleft of DNMT1.

fC7’ is looped out of the helix and inserted into the catalytic pocket of methyltransferase domain. By forming a covalent bond with Cys1229 residue. fC7' anchored at specific position within the catalytic core of the methytransferase domain and it is surrounded by other strictly conserved residues in the catalytic core.

The carbon 5-methyl group of mC6 in the parental strand forms Van der Waal's interaction with the hydrophobic domain of the TRD domain and directs the parental strand to the TRD.

Particularly, the indole ring of Try1512 slides into the DNA major groove upon complex formation and the indole ring is partially stacked with the base of m6C.

Together with other hydrophobic residues(cys 1501,Leu 1515, and Met1535), forms a shallow concave surface harbouring the 5-methyl group of  mC6.

The specific interaction with fC7' in the target strand explains the intrinsic substrate preference of DNMT1 towards hemi-mCpG DNA substrates.

Additionally, an autoinhibitory mechanism performed by DNMT-1 have been discovered which further prevents methylation on unmethylated CpG dinucleotides duplex DNA.