Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences

Priyamvada Rai, David E. Wemmer, Stuart Linn

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Certain DNA sequences are known to be unusually sensitive to nicking via the Fe2+-mediated Fenton reaction. Most notable are a purine nucleotide followed by three or more G residues, RGGG, and purine nucleotides flanking a TG combination, RTGR. Our laboratory previously demonstrated that nicking in the RGGG sequences occurs preferentially 5′ to a G residue with the nicking probability decreasing from the 5′ to 3′end of these sequences. Using 1H NMR to characterize Fe2+ binding within the duplex CGAGTTAGGGTAGC/GCTACCCTAACTCG and 7-deazaguanine-containing (Z) variants of it, we show that Fe2+ binds preferentially at the GGG sequence, most strongly towards its 5′ end. Substitutions of individual guanines with Z indicate that the high affinity Fe2+ binding at AGGG involves two adjacent guanine N7 moieties. Binding is accompanied by large changes in specific imino, aromatic and methyl proton chemical shifts, indicating that a locally distorted structure forms at the binding site that affects the conformation of the two base pairs 3′ to the GGG sequence. The binding of Fe2+ to RGGG contrasts with that previously observed for the RTGR sequence, which binds Fe2+ with negligible structural rearrangements.

Original languageEnglish
Pages (from-to)497-510
Number of pages14
JournalNucleic Acids Research
Volume33
Issue number2
DOIs
StatePublished - Mar 29 2005
Externally publishedYes

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Purine Nucleotides
Guanine
Base Pairing
Protons
Binding Sites
Proton Magnetic Resonance Spectroscopy
7-deazaguanine

ASJC Scopus subject areas

  • Genetics

Cite this

Preferential binding and structural distortion by Fe2+ at RGGG-containing DNA sequences correlates with enhanced oxidative cleavage at such sequences. / Rai, Priyamvada; Wemmer, David E.; Linn, Stuart.

In: Nucleic Acids Research, Vol. 33, No. 2, 29.03.2005, p. 497-510.

Research output: Contribution to journalArticle

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