MBD4 glycosylase mediated recognition and binding of a thymine opposite to a guanine at CpG sequences

Stable Identifier
R-HSA-110172
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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MBD4 (MED1; methyl-CpG-binding domain protein 4) recognizes and binds thymine mispaired with guanine in CpG islands. G:T mispair is generated by oxidative deamination of 5-methylcytosine (Petronzelli et al. 2000). MBD4 contains two DNA binding domains: an N-terminal methyl-CpG binding domain (MBD) and a C-terminal mismatch-specific glycosylase domain (Wu et al. 2003). MBD4 catalytic domain uses a flipping mechanism to extrude the thymine from the helix and thereby detect G:T mispairs (Morera et al. 2012).

Literature References
PubMed ID Title Journal Year
10930409 Biphasic kinetics of the human DNA repair protein MED1 (MBD4), a mismatch-specific DNA N-glycosylase

Petronzelli, F, Riccio, A, Markham, GD, Seeholzer, SH, Stoerker, J, Genuardi, M, Yeung, AT, Matsumoto, Y, Bellacosa, A

J. Biol. Chem. 2000
12456671 Mismatch repair in methylated DNA. Structure and activity of the mismatch-specific thymine glycosylase domain of methyl-CpG-binding protein MBD4

Wu, P, Qiu, C, Sohail, A, Zhang, X, Bhagwat, AS, Cheng, X

J. Biol. Chem. 2003
22848106 Biochemical and structural characterization of the glycosylase domain of MBD4 bound to thymine and 5-hydroxymethyuracil-containing DNA

Moréra, S, Grin, I, Vigouroux, A, Couvé, S, Henriot, V, Saparbaev, M, Ishchenko, AA

Nucleic Acids Res. 2012
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