Recognition of 5-Hydroxymethylcytosine by the Uhrf1 SRA Domain

被引：136

作者：

Frauer, Carina ^{[1
,4
]}

Hoffmann, Thomas ^{[2
,4
]}

Bultmann, Sebastian ^{[1
,4
]}

Casa, Valentina ^{[3
]}

Cardoso, M. Cristina ^{[3
]}

Antes, Iris ^{[2
,4
]}

Leonhardt, Heinrich ^{[1
,4
]}

机构：

[1] Univ Munich, Dept Biol 2, Planegg Martinsried, Germany

[2] Tech Univ Munich, Dept Life Sci, D-8050 Freising Weihenstephan, Germany

[3] Tech Univ Darmstadt, Dept Biol, Darmstadt, Germany

[4] Ctr Integrated Prot Sci Munich CIPSM, Munich, Germany

来源：

PLOS ONE | 2011年 / 6卷 / 06期

关键词：

HEMI-METHYLATED DNA; MOLECULAR-DYNAMICS; METHYLTRANSFERASE; BINDING; 5-METHYLCYTOSINE; PROTEINS; CONVERSION; MUTATION; DNMT3A; DAMAGE;

D O I：

10.1371/journal.pone.0021306

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：8

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