Dynamic opening of DNA during the enzymatic search for a damaged base.

Chunyang Cao, Yu Lin Jiang, James Stivers, Fenhong Song

Research output: Contribution to journalArticle

Abstract

Uracil DNA glycosylase (UDG) removes uracil from U.A or U.G 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.

Original languageEnglish (US)
Pages (from-to)1230-1236
Number of pages7
JournalNature structural & molecular biology
Volume11
Issue number12
StatePublished - Dec 2004

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Uracil-DNA Glycosidase
Base Pairing
Uracil
DNA
B-Form DNA
Theophylline
DNA Repair
Protons
Genome

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Dynamic opening of DNA during the enzymatic search for a damaged base. / Cao, Chunyang; Jiang, Yu Lin; Stivers, James; Song, Fenhong.

In: Nature structural & molecular biology, Vol. 11, No. 12, 12.2004, p. 1230-1236.

Research output: Contribution to journalArticle

Cao, Chunyang ; Jiang, Yu Lin ; Stivers, James ; Song, Fenhong. / Dynamic opening of DNA during the enzymatic search for a damaged base. In: Nature structural & molecular biology. 2004 ; Vol. 11, No. 12. pp. 1230-1236.
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