DNMT1 methylates cytosine in hemimethylated DNA

Stable Identifier
R-HSA-5334151
Type
Reaction [transition]
Species
Homo sapiens
Compartment
nucleoplasm
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
DNMT1 methylates cytosine in hemimethylated DNA
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
21163962 Structure of DNMT1-DNA complex reveals a role for autoinhibition in maintenance DNA methylation

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

Science 2011
24368767 The UHRF1 Protein Stimulates the Activity and Specificity of the Maintenance DNA Methyltransferase DNMT1 by an Allosteric Mechanism

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

J. Biol. Chem. 2014
10551868 Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation

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

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

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

Science 2007
18302924 Cytosine methylation: remaining faithful

Ooi, SK, Bestor, TH

Curr. Biol. 2008
Participants
Input
Output
Participates
as an event of
Catalyst Activity

DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates of DNMT1:UHRF1:Chromatin with hemimethylC [nucleoplasm]

Physical Entity
DNMT1:UHRF1:Chromatin with hemimethylC [nucleoplasm] (Homo sapiens)
Activity
DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates (GO:0051718)
Inferred From
Dnmt1 methylates cytosine in hemimethylated DNA (Mus musculus)
Authored
May, B  (2014-02-21)
Reviewed
Martín-Subero, JI  (2014-07-24)
Beekman, R  (2014-07-24)
Created
May, B  (2014-02-22)
Cite Us!