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Frauer, Carina; Hoffmann, Thomas; Bultmann, Sebastian; Casa, Valentina; Cardoso, M. Cristina; Antes, Iris; Leonhardt, Heinrich (2011): Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.
In: PloS one 6(6), e21306




Recent discovery of 5-hydroxymethylcytosine (5hmC) in genomic DNA raises the question how this sixth base is recognized by cellular proteins. In contrast to the methyl-CpG binding domain (MBD) of MeCP2, we found that the SRA domain of Uhrf1, an essential factor in DNA maintenance methylation, binds 5hmC and 5-methylcytosine containing substrates with similar affinity. Based on the co-crystal structure, we performed molecular dynamics simulations of the SRA:DNA complex with the flipped cytosine base carrying either of these epigenetic modifications. Our data indicate that the SRA binding pocket can accommodate 5hmC and stabilizes the flipped base by hydrogen bond formation with the hydroxyl group.