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Structure and hemimethylated CpG binding of the SRA domain from human UHRF1.

ABSTRACT: Human UHRF1 (ubiquitin-like PHD and RING finger 1) functions to maintain CpG DNA methylation patterns through DNA replication by co-localizing with the DNA methyltransferase DNMT1 at chromatin in mammals. Recent studies show that UHRF1 binds selectively to hemimethylated CpG via its conserved SRA (SET- and RING finger-associated) domain. However, the underlying molecular mechanism is not known. Here, we report a 1.95 A resolution crystal structure of the SRA domain of human UHRF1. Using NMR structure-guided mutagenesis, electrophoretic mobility shift assay, and fluorescence anisotropy analysis, we determined key amino acid residues for methyl-DNA binding that are conserved in the SRA domain.

SUBMITTER: Qian C

PROVIDER: S-EPMC2596396 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature

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Structure and hemimethylated CpG binding of the SRA domain from human UHRF1.

Qian Chengmin C Li Side S Jakoncic Jean J Zeng Lei L Walsh Martin J MJ Zhou Ming-Ming MM

The Journal of biological chemistry 20081022 50

Human UHRF1 (ubiquitin-like PHD and RING finger 1) functions to maintain CpG DNA methylation patterns through DNA replication by co-localizing with the DNA methyltransferase DNMT1 at chromatin in mammals. Recent studies show that UHRF1 binds selectively to hemimethylated CpG via its conserved SRA (SET- and RING finger-associated) domain. However, the underlying molecular mechanism is not known. Here, we report a 1.95 A resolution crystal structure of the SRA domain of human UHRF1. Using NMR stru ...[more]

PMID: 18945682

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