title: Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain.
abstract: 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.
authors: Department of Biology II, Ludwig Maximilians University Munich, Planegg-Martinsried, Germany.
authors: Carina
authors: C
authors: Frauer
authors: Thomas
authors: T
authors: Hoffmann
authors: Sebastian
authors: S
authors: Bultmann
authors: Valentina
authors: V
authors: Casa
authors: M Cristina
authors: MC
authors: Cardoso
authors: Iris
authors: I
authors: Antes
authors: Heinrich
authors: H
authors: Leonhardt
mesh_terms: D044503:5-Methylcytosine / Q000378:metabolism / Q000031:analogs & derivatives; D001665:Binding Sites; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D018899:CpG Islands / Q000235:genetics; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D013816:Thermodynamics
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine; D004247:DNA