DNA adduct structure-function relationships: Comparing solution with polymerase structures

Suse Broyde, Lihua Wang, Ling Zhang, Olga Rechkoblit, Nicholas E. Geacintov, Dinshaw J. Patel

Research output: Contribution to journalReview article

Abstract

It has now been nearly two decades since the first solution structures of DNA duplexes covalently damaged by metabolically activated polycyclic aromatic hydrocarbons and amines were determined by NMR. Dozens of such high-resolution structures are now available, and some broad structural themes have been uncovered. It has been hypothesized that the solution structures are relevant to the biochemical processing of the adducts. The structural features of the adducts are considered to determine their mutational properties in DNA polymerases and their repair susceptibilities. In recent years, a number of crystal structures of DNA adducts of interest to our work have been determined in DNA polymerases. Accordingly, it is now timely to consider how NMR solution structures relate to structures within DNA polymerases. The NMR solution structural themes for polycyclic aromatic adducts are often observed in polymerase crystal structures. While the polymerase interactions can on occasion override the solution preferences, intrinsic adduct conformations favored in solution are often manifested within polymerases and likely play a significant role in lesion processing.

Original languageEnglish (US)
Pages (from-to)45-52
Number of pages8
JournalChemical research in toxicology
Volume21
Issue number1
DOIs
StatePublished - Jan 2008

ASJC Scopus subject areas

  • Toxicology

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