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. Author manuscript; available in PMC: 2009 Jan 21.
Published in final edited form as: Cell. 2008 Dec 26;135(7):1201–1212. doi: 10.1016/j.cell.2008.11.042

Figure 7. Model for 5-meC Demethylation.

Figure 7

Demethylation may occur through a two-step coupled enzymatic process, promoted by Gadd45. The first enzymatic step involves deamination of 5-meC by AID (amine group removed, in blue), generating a thymine product and a G:T mismatch. The second step involves thymine base removal by Mdb4, generating an abasic site. As the transient G:T intermediate is not detected in cells with active Mbd4, but is with catalytically inactive Mbd4, the thymine is likely rapidly removed, suggesting a coupling between deaminase and glycosylase activity. Gadd45 may promote functional or physical interactions between AID and Mbd4 at the site of demethylation. Mbd4 may couple with a lyase to help promote base replacement through base excision repair (neither shown nor addressed). Targeting of AID/Mbd4 may be promoted by recognition of the 5-meCpG (methyl group in red), or through other mechanisms (data not shown).