A review of the role of the sequence-dependent electrostatic landscape in DNA alkylation patterns

Barry Gold, Luis M. Marky, Michael P. Stone, Loren D. Williams

Research output: Contribution to journalReview article

23 Scopus citations

Abstract

Alkylating agents, including environmental and endogenous carcinogens and DNA targeting antineoplastic agents, that adduct DNA via intermediates with significant cationic charge show a sequence selectively in their covalent bonding to nucleobases. The resulting patterns of alkylation eventually contribute to the agent-dependent distributions and types of mutations. The origin of the regioselective modification of DNA by electrophiles has been attributed to steric and/or electronic factors, but attempts to mechanistically model and predict alkylation patterns have had limited success. In this review, we present data consistent with the role of the intrinsic sequence-dependent electrostatic landscape (SDEL) in DNA that modulates the equilibrium binding of cations and the bonding of reactive charged alkylating agents to atoms that line the floor of the major groove of DNA.

Original languageEnglish (US)
Pages (from-to)1402-1414
Number of pages13
JournalChemical Research in Toxicology
Volume19
Issue number11
DOIs
StatePublished - Nov 2006

ASJC Scopus subject areas

  • Toxicology

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