Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications

Ernst S. Henle, Zhengxu Han, Ning Tang, Priyamvada Rai, Yongzhang Luo, Stuart Linn

Research output: Contribution to journalArticle

255 Citations (Scopus)

Abstract

Preferential cleavage sites have been determined for Fe2+/H2O2- mediated oxidations of DNA. In 50 mM H2O2, preferential cleavages occurred at the nucleoside 5' to each of the dG moieties in the sequence RGGG, a sequence found in a majority of telomere repeats. Within a plasmid containing a (TTAGGG)81 human telomere insert, 7-fold more strand breakage occurred in the restriction fragment with the insert than in a similar-sized control fragment. This result implies that telomeric DNA could protect coding DNA from oxidative damage and might also link oxidative damage and iron load to telomere shortening and aging. In micromolar H2O2, preferential cleavage occurred at the thymidine within the sequence RTGR, a sequence frequently found to be required in promoters for normal responses of many procaryotic and eucaryotic genes to iron or oxygen stress. Computer modeling of the interaction of Fe2+ with RTGR in B-DNA suggests that due to steric hindrance with the thymine methyl, Fe2+ associates in a specific manner with the thymine flipped out from the base stack so as to allow an octahedrally-oriented coordination of the Fe2+ with the three purine N7 residues. Fe2+-dependent changes in NMR spectra of duplex oligonucleotides containing ATGA versus those containing AUGA or A(5m)CGA were consistent with this model.

Original languageEnglish
Pages (from-to)962-971
Number of pages10
JournalJournal of Biological Chemistry
Volume274
Issue number2
DOIs
StatePublished - Jan 8 1999
Externally publishedYes

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DNA Cleavage
Thymine
Telomere
Iron
B-Form DNA
Telomere Shortening
DNA
Nucleosides
Oligonucleotides
Thymidine
DNA Damage
Plasmids
Oxygen
Genes
Aging of materials
Nuclear magnetic resonance
Oxidation
purine

ASJC Scopus subject areas

  • Biochemistry

Cite this

Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. / Henle, Ernst S.; Han, Zhengxu; Tang, Ning; Rai, Priyamvada; Luo, Yongzhang; Linn, Stuart.

In: Journal of Biological Chemistry, Vol. 274, No. 2, 08.01.1999, p. 962-971.

Research output: Contribution to journalArticle

Henle, Ernst S. ; Han, Zhengxu ; Tang, Ning ; Rai, Priyamvada ; Luo, Yongzhang ; Linn, Stuart. / Sequence-specific DNA cleavage by Fe2+-mediated fenton reactions has possible biological implications. In: Journal of Biological Chemistry. 1999 ; Vol. 274, No. 2. pp. 962-971.
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