Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain

Carina Frauer; Thomas Hoffmann; Sebastian Bultmann; Valentina Casa; M. Cristina Cardoso; Iris Antes; Heinrich Leonhardt

doi:10.1371/journal.pone.0021306

Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain

Carina Frauer, Thomas Hoffmann, Sebastian Bultmann, Valentina Casa, M. Cristina Cardoso, Iris Antes, Heinrich Leonhardt

Associate Professorship of Protein Modelling

Research output: Contribution to journal › Article › peer-review

156 Scopus citations

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.

Original language	English
Article number	e21306
Journal	PLoS ONE
Volume	6
Issue number	6
DOIs	https://doi.org/10.1371/journal.pone.0021306
State	Published - 2011

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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.",

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AU - Cardoso, M. Cristina

AU - Antes, Iris

AU - Leonhardt, Heinrich

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AB - 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.

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Recognition of 5-hydroxymethylcytosine by the Uhrf1 SRA domain

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