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5-Formylcytosine does not change the global structure of DNA

DOI: 10.1038/nsmb.3411 DOI Help

Authors: Jack S. Hardwick (University of Oxford) , Denis Ptchelkine (Research Complex at Harwell) , Afaf H. El-sagheer (University of Oxford) , Ian Tear (University of Southampton) , Daniel Singleton (University of Southampton) , Simon E. V. Phillips (Research Complex at Harwell) , Andrew N. Lane (University of Kentucky) , Tom Brown (University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Structural & Molecular Biology , VOL 74

State: Published (Approved)
Published: May 2017

Abstract: The mechanism by which the recently identified DNA modification 5-formylcytosine (fC) is recognized by epigenetic writer and reader proteins is not known. Recently, an unusual DNA structure, F-DNA, has been proposed as the basis for enzyme recognition of clusters of fC. We used NMR and X-ray crystallography to compare several modified DNA duplexes with unmodified analogs and found that in the crystal state the duplexes all belong to the A family, whereas in solution they are all members of the B family. We found that, contrary to previous findings, fC does not significantly affect the structure of DNA, although there are modest local differences at the modification sites. Hence, global conformation changes are unlikely to account for the recognition of this modified base, and our structural data favor a mechanism that operates at base-pair resolution for the recognition of fC by epigenome-modifying enzymes.

Journal Keywords: DNA methylation; Gene silencing; NMR spectroscopy; X-ray crystallography

Subject Areas: Biology and Bio-materials

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-Macromolecular Crystallography