Dnmt1 methylates cytosine in hemimethylated DNA

Stable Identifier
R-MMU-5336369
Type
Reaction [transition]
Species
Mus musculus
Compartment
General
SVG |   | PPTX  | SBGN
Dnmt1 methylates cytosine in hemimethylated DNA

Dnmt1 transfers a methyl group from S-adenosylmethionine to the 5-position of the cytosine ring of cytosine residues in DNA. Dnmt1 contains a catalytic C-terminal domain and an N-terminal regulatory domain (Bestor et al. 1988), and alone has an approximately 15-fold preference for methylating hemimthylated CG dinucleotides relative to unmethylated dinucleotides in DNA (Bestor and Ingram 1983, Gowher et al. 2005, Svedruzic et al. 2005, Vilkaitis et al. 2005, Goyal et al. 2006). Interaction with Uhrf1 (Np95) specifically increases the activity of Dnmt1 on hemimethylated DNA (Berkyurek et al. 2014). Structural analysis indicates that the hemimethylated cytosine residue is bound to a shallow hydrophobic concave surface of Dnmt1 while the substrate cytosine is covalently bound to the catalytic pocket (Song et al. 2012).

Literature References
PubMed ID Title Journal Year
16500889 Accuracy of DNA methylation pattern preservation by the Dnmt1 methyltransferase

Goyal, R, Reinhardt, R, Jeltsch, A

Nucleic Acids Res. 2006
22323818 Structure-based mechanistic insights into DNMT1-mediated maintenance DNA methylation

Song, J, Teplova, M, Ishibe-Murakami, S, Patel, DJ

Science 2012
16274244 Mechanism of allosteric regulation of Dnmt1's processivity

Svedruzi?, ZM, Reich, NO

Biochemistry 2005
15509558 Processive methylation of hemimethylated CpG sites by mouse Dnmt1 DNA methyltransferase

Vilkaitis, G, Suetake, I, Klimasauskas, S, Tajima, S

J. Biol. Chem. 2005
3210246 Cloning and sequencing of a cDNA encoding DNA methyltransferase of mouse cells. The carboxyl-terminal domain of the mammalian enzymes is related to bacterial restriction methyltransferases

Bestor, T, Laudano, A, Mattaliano, R, Ingram, V

J. Mol. Biol. 1988
6577443 Two DNA methyltransferases from murine erythroleukemia cells: purification, sequence specificity, and mode of interaction with DNA

Bestor, TH, Ingram, VM

Proc. Natl. Acad. Sci. U.S.A. 1983
16026162 De novo methylation of nucleosomal DNA by the mammalian Dnmt1 and Dnmt3A DNA methyltransferases

Gowher, H, Stockdale, CJ, Goyal, R, Ferreira, H, Owen-Hughes, T, Jeltsch, A

Biochemistry 2005
24253042 The DNA methyltransferase Dnmt1 directly interacts with the SET and RING finger-associated (SRA) domain of the multifunctional protein Uhrf1 to facilitate accession of the catalytic center to hemi-methylated DNA

Berkyurek, AC, Suetake, I, Arita, K, Takeshita, K, Nakagawa, A, Shirakawa, M, Tajima, S

J. Biol. Chem. 2014
Participants
Catalyst Activity
Catalyst Activity
Title
DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates of Dnmt1:Uhrf1:Chromatin with hemimethylC [nucleoplasm]
Physical Entity
Activity
Orthologous Events
Authored
Reviewed
Created