title: 5-Formylcytosine alters the structure of the DNA double helix.
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.
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Eun-Ang
authors.initials: EA
authors.lastname: Raiber
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.
authors.forename: Pierre
authors.initials: P
authors.lastname: Murat
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Dimitri Y
authors.initials: DY
authors.lastname: Chirgadze
authors.affiliation: Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.
authors.forename: Dario
authors.initials: D
authors.lastname: Beraldi
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge, UK.
authors.forename: Ben F
authors.initials: BF
authors.lastname: Luisi
authors.affiliation: Department of Chemistry, University of Cambridge, Cambridge, UK.|Cancer Research UK Cambridge Institute, Li Ka Shing Centre, Cambridge, UK.|School of Clinical Medicine, University of Cambridge, Cambridge, UK.
authors.forename: Shankar
authors.initials: S
authors.lastname: Balasubramanian
mesh_terms: D055592:Biophysical Phenomena; D018360:Crystallography, X-Ray; D003596:Cytosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: C560973:5-formylcytosine; D003596:Cytosine; D004247:DNA