Guanine-specific DNA damage induced by gamma-irradiated histone

Research output: Contribution to journalJournal articleResearchpeer-review

Ayako Furukawa, Yusuke Hiraku, Shinji Oikawa, Catherine Luxford, Michael Jonathan Davies, Shosuke Kawanishi

In gamma-irradiation, *OH is directly generated from water and causes DNA damage leading to carcinogenesis. Exposure of proteins to gamma-irradiation, in the presence of oxygen, gives high yields of hydroperoxides. To clarify whether these hydroperoxides, particularly those formed on DNA-binding histone proteins, participate in gamma-irradiation-induced carcinogenesis, experiments using 32P-labelled DNA fragments obtained from human cancer-related genes were undertaken. Histone protein-hydroperoxides induced significant DNA damage in the presence of Cu(I). Histone H1- and H3-hydroperoxides showed stronger DNA damage compared with histone H2A- and H4-hydroperoxides at 0.7 muM. Histone H1-hydroperoxides caused Cu(I)-dependent DNA damage predominantly at guanine residues, especially at 5'-GGC-3', 5'-GGA-3', 5'-GGT-3' and single G bases. In contrast, histone H3-hydroperoxides/Cu(I) induced DNA damage at 5'-G in GG sequences; this sequence specificity is identical with that generated by 2,2'-azobis (2-amidinopropane) dihydrochloride, which is known to produce peroxyl radicals (RO2*). The difference in site specificity of DNA damage induced by histone H1- and H3-hydroperoxides may arise from their amino acid composition or their mode of binding to DNA. The histone H1-hydroperoxides/Cu(I) system also induced 8-oxo-7,8-dihydro-2'-deoxyguanosine formation in calf thymus DNA. It is concluded that histone protein-hydroperoxides can induce guanine-specific DNA damage, which may contribute to gamma-irradiation-induced carcinogenesis.

Original languageEnglish
JournalBiochemical Journal
Volume388
Issue numberPt 3
Pages (from-to)813-8
Number of pages6
ISSN0264-6021
DOIs
Publication statusPublished - 15 Jun 2005
Externally publishedYes

    Research areas

  • Amidines, Animals, Cattle, Copper, DNA, DNA Damage, Deoxyguanosine, Gamma Rays, Genes, p53, Genes, ras, Guanine, Histones, Humans, Hydrogen Peroxide, Oxidation-Reduction

ID: 129672056