DNMT1 methylates cytosine in hemimethylated DNA

Stable Identifier
R-HSA-5334151
Type
Reaction [transition]
Species
Homo sapiens
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DNMT1 transfers a methyl group from S-adenosylmethionine to the 5-position of the cytosine ring of cytosine residues in DNA. Purified human DNMT1 shows a 7 to 21-fold preference for hemimethylated CG motifs in DNA compared to unmethylated CG motifs (Pradhan et al. 1999) thus DNMT1 tends to maintain existing methylation through DNA replication. The binding of the CXXC motif of DNMT1 to cytosine in symmetrically unmethylated CG dinucleotides prevents access of cytosine to the active site and thereby prevents de novo methylation (Song et al. 2011). UHRF1 binds hemimethylated DNA and histone H3 tails methylated at lysine-9 and recruits DNMT1 to methylate hemimethylated DNA (Bostick et al. 2007, reviewed in Ooi and Bestor 2008). Interaction of UHRF1 with DNMT1 increases the methylation activity of DNMT1 about 5-fold (Bashtrykov et al. 2014).

Literature References
PubMed ID Title Journal Year
24368767 The UHRF1 Protein Stimulates the Activity and Specificity of the Maintenance DNA Methyltransferase DNMT1 by an Allosteric Mechanism

Bashtrykov, P, Jankevicius, G, Jurkowska, RZ, Ragozin, S, Jeltsch, A

J. Biol. Chem. 2014
21163962 Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation

Song, J, Rechkoblit, O, Bestor, TH, Patel, DJ

Science 2011
10551868 Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation

Pradhan, S, Bacolla, A, Wells, RD, Roberts, RJ

J Biol Chem 1999
17673620 UHRF1 plays a role in maintaining DNA methylation in mammalian cells

Bostick, M, Kim, JK, Estève, PO, Clark, A, Pradhan, S, Jacobsen, SE

Science 2007
18302924 Cytosine methylation: remaining faithful

Ooi, SK, Bestor, TH

Curr. Biol. 2008
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Catalyst Activity
Title
DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates of DNMT1:UHRF1:Chromatin with hemimethylC [nucleoplasm]
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