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5-Formylcytosine alters the structure of the DNA double helix

DOI: 10.1038/nsmb.2936 DOI Help

Authors: Eun-ang Raiber (University of Cambridge) , Pierre Murat (University of Cambridge) , Dima Chirgadze (University of Cambridge) , Dario Beraldi (University of Cambridge) , Ben Luisi (Department of Biochemistry, University of Cambridge) , Shankar Balasubramanian (University of Cambridge)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 22 (1) , PAGES 44 - 49

State: Published (Approved)
Published: December 2014

Open Access Open Access

Abstract: The modified base 5-formylcytosine (5fC) was recently identified in mammalian DNA and might be considered to be the 'seventh' base of the genome. This nucleotide has been implicated in active demethylation mediated by the base excision repair enzyme thymine DNA glycosylase. Genomics and proteomics studies have suggested an additional role for ​5fC in transcription regulation through chromatin remodeling. Here we propose that 5fC might affect these processes through its effect on DNA conformation. Biophysical and structural analysis revealed that 5fC alters the structure of the DNA double helix and leads to a conformation unique among known DNA structures including those comprising other cytosine modifications. The 1.4-Å-resolution X-ray crystal structure of a DNA dodecamer comprising three 5fCpG sites shows how 5fC changes the geometry of the grooves and base pairs associated with the modified base, leading to helical underwinding.

Subject Areas: Chemistry

Instruments: I24-Microfocus Macromolecular Crystallography

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