5-methylcytosine G/T mismatch specific DNA glycosylase mediated recognition and binding of thymine opposite guanine at CpG sequences

Stable Identifier
R-GGA-353481
Type
Reaction [transition]
Species
Gallus gallus
Compartment
ReviewStatus
5/5
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5-methylcytosine G/T mismatch specific DNA glycosylase is the chicken homolog of the human MBD4 G/T mismatch DNA glycosylase. The chicken enzyme shows 46% identity with human MBD4, while the conserved catalytic region contained within 170 amino acids at the C terminal end has 90% identity. The non conserved region of the avian protein does not apparently contain a consensus sequence found in known methylated DNA binding domains. The 5-methylcytosine G/T mismatch specific glycosylase specifically recognizes the thymine coupled to guanine at methylated CpG sequences, and can both remove the thymine residue and demethylate the C residue. The recombinant proteins from human and chicken have G/T mismatch as well as 5-methylcytosine (5-MeC) DNA glycosylase activities. The enzyme has only 5-MeC DNA glycosylase activity with the hemimethylated DNA although binds equally well to symmetrically methylated DNA or non methylated DNA. Deletion mutations show that G/T mismatch and 5-MeC DNA glycosylase are located in the C-terminal conserved region. In sharp contrast to the 5-MeC DNA glycosylase isolated from the chicken embryo DNA demethylation complex, the two enzymatic activities of human MBD4 are strongly inhibited by RNA.

Literature References
PubMed ID Title Journal Year
11058112 5-Methylcytosine DNA glycosylase activity is also present in the human MBD4 (G/T mismatch glycosylase) and in a related avian sequence

Siegmann, M, Thiry, S, Angliker, H, Schwarz, S, Zhu, B, Zheng, Y, Jost, JP

Nucleic Acids Res 2000
7730351 Mechanisms of DNA demethylation in chicken embryos. Purification and properties of a 5-methylcytosine-DNA glycosylase

Sun, L, Siegmann, M, Leung, R, Jost, JP

J Biol Chem 1995
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Catalyst Activity

DNA N-glycosylase activity of TDG [nucleoplasm]

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