Oxidative damage to a supercoiled DNA by water soluble peroxyl radicals characterized with DNA repair enzymes

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DOIResolve DOI: http://doi.org/10.1021/tx030024u
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TypeArticle
Journal titleChemical Research in Toxicology
ISSN0893228X
Volume16
Issue9
Pages11181123; # of pages: 6
AbstractEarlier work (Paul, T., et al. (2000) Biochemistry 39, 4129-4135) has demonstrated that the water soluble positively charged peroxyl radical, (H2N)2+CC(CH3)2OO (+AOO), caused direct strand scission of the Escherichia coli plasmid supercoiled DNA, pBR 322, with ca. 50% scission occurring at a +AOO/base pair (bp) ratio of 0.2. There was no measurable direct scission with a negatively charged peroxyl (-BOO) at -BOO/bp = 24, nor with a neutral peroxyl (COO) at COO/bp = 5. Base modification (BM) of the same DNA by the same peroxyls has now been investigated using four base excision repair (BER) glycosylases. At +AOO/bp = 0.04, there is 10% direct strand scission, and the Fpg protein recognized an additional 25% BM, while endonuclease (Endo) IV recognized an additional 20% BM and the other two BER enzymes did not give statistically significant BMs. None of the BER enzymes showed BMs in the DNA treated with -BOO. However, Fpg and Endo IV showed that at COO/bp = 3.4 there was a BM comparable to that observed at +AOO/bp = 0.04. Thus, COO radicals are only ca. 1.2% as reactive toward the DNA's bases as +AOO. These results underline the importance of Coulombic forces in DNA reactions. It is also proposed that +AOO has a higher intrinsic reactivity in H-atom abstractions and electron transfer processes than -BOO or COO radicals.
Publication date
AffiliationNational Research Council Canada
Peer reviewedNo
Identifier10439298
NPARC number12339240
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Record identifier5a18eb70-bc2c-45a9-955e-c3aabc1c4c16
Record created2009-09-11
Record modified2016-05-09
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