Nature Structural & Molecular Biology11, 1230 - 1236 (2004)
Published online: 21 November 2004; | doi:10.1038/nsmb864
Dynamic opening of DNA during the enzymatic search for a damaged base
Chunyang Cao1, Yu Lin Jiang1, James T Stivers1
& Fenhong Song2
1
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, Maryland 21205, USA.
2
Center for Advanced Research in Biotechnology of the National Institute of Standards and Technology and the University of Maryland Biotechnology Institutes, 9600 Gudelsky Drive, Rockville, Maryland 20850, USA.
Uracil DNA glycosylase (UDG) removes uracil from UA or UG base pairs in genomic DNA by extruding the aberrant uracil from the DNA base stack. A question in enzymatic DNA repair is whether UDG and related glycosylases also use an extrahelical recognition mechanism to inspect the integrity of undamaged base pairs. Using NMR imino proton exchange measurements we find that UDG substantially increases the equilibrium constant for opening of T-A base pairs by almost two orders of magnitude relative to free B-DNA. This increase is brought about by enzymatic stabilization of an open state of the base pair without increasing the rate constant for spontaneous base pair opening. These findings indicate a passive search mechanism in which UDG uses the spontaneous opening dynamics of DNA to inspect normal base pairs in a rapid genome-wide search for uracil in DNA.
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