Functional characterisation of AlkB-like macromolecular demethylases

We have recently discovered a novel mechanism for repairing methylation damage in DNA and RNA. The repair reaction occurs by oxidative demethylation, and can be performed both by human and bacterial AlkB proteins. Eight different AlkB-like proteins are fo und in the human genome, and the project will focus on three such proteins, denoted hABH4, hABH6, and hABH8, which are all conserved across the animal kingdom. hABH8 contains, in addition to an AlkB domain, a domain with strong homology to tRNA methylases . This may suggest that hABH8 may be a combined tRNA demethylase/methylase involved in controlling protein translation by regulating tRNA modification levels. Protein interaction studies suggest that hABH4 and hABH6 may be involved in regulating transcrip tion. Thus, the current knowledge suggests that hABH4, hABH6, and hABH8, rather than being involved in repair, may be responsible for other cellular demethylation reactions, and the project is aimed at elucidating the function of these proteins.