Photosensitized oxidative DNA damage: From hole injection to chemical product formation and strand cleavage

Byeong Hwa Yun, Young Ae Lee, Seog K. Kim, Vladimir Kuzmin, Alexander Kolbanovskiy, Peter C. Dedon, Nicholas Geacintov, Vladimir Shafirovich

Research output: Contribution to journalArticle

Abstract

Oxidatively generated damage to DNA induced by a pyrenyl photosensitizer residue (Py) covalently attached to a guanine base in the DNA sequence context 5′-d(CAT[G1Py]CG2TCCTAC) in aerated solutions was monitored from the initial one-electron transfer, or hole injection step, to the formation of chemical end-products monitored by HPLC, mass spectrometry, and high-resolution gel electrophoresis. Hole injection into the DNA was initiated by two-photon excitation of the Py residue with 355 nm laser pulses, thus producing the radical cation Py•+ and hydrated electrons; the latter are trapped by O2, thus forming the superoxide anion O2•+. The decay of the Py •+ radical is correlated with the appearance of the G •+/G(-H) radical on microsecond time scales, and O2•- combines with guanine radicals at G 1 to form alkali-labile 2,5-diamino-4H-imidazolone lesions (Iz 1Py). Product formation in the modified strand is smaller by a factor of 2.4 in double-stranded than in single-stranded DNA. In double-stranded DNA, hot piperidine-mediated cleavage at G2 occurs only after G1Py, an efficient hole trap, is oxidized thus generating tandem lesions. An upper limit of hole hopping rates, khh < 5 × 103 s-1 from G1 •+-Py to G2 can be estimated from the known rates of the combination reaction of the G(-H) and O2 •- radicals. The formation of Iz products in the unmodified complementary strand compared to the modified strand in the duplex is ∼10 times smaller. The formation of tandem lesions is observed even at low levels of irradiation corresponding to "single-hit" conditions when less than ∼10% of the oligonucleotide strands are damaged. A plausible mechanism for this observation is discussed.

Original languageEnglish (US)
Pages (from-to)9321-9332
Number of pages12
JournalJournal of the American Chemical Society
Volume129
Issue number30
DOIs
StatePublished - Aug 1 2007

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Guanine
DNA Damage
DNA
Electrons
Photosensitizing Agents
Single-Stranded DNA
Alkalies
Photons
Oligonucleotides
Superoxides
Hole traps
Electrophoresis
Cations
Mass Spectrometry
Lasers
Gels
DNA sequences
High Pressure Liquid Chromatography
Photosensitizers
Mass spectrometry

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Yun, B. H., Lee, Y. A., Kim, S. K., Kuzmin, V., Kolbanovskiy, A., Dedon, P. C., ... Shafirovich, V. (2007). Photosensitized oxidative DNA damage: From hole injection to chemical product formation and strand cleavage. Journal of the American Chemical Society, 129(30), 9321-9332. https://doi.org/10.1021/ja066954s

Photosensitized oxidative DNA damage : From hole injection to chemical product formation and strand cleavage. / Yun, Byeong Hwa; Lee, Young Ae; Kim, Seog K.; Kuzmin, Vladimir; Kolbanovskiy, Alexander; Dedon, Peter C.; Geacintov, Nicholas; Shafirovich, Vladimir.

In: Journal of the American Chemical Society, Vol. 129, No. 30, 01.08.2007, p. 9321-9332.

Research output: Contribution to journalArticle

Yun, Byeong Hwa ; Lee, Young Ae ; Kim, Seog K. ; Kuzmin, Vladimir ; Kolbanovskiy, Alexander ; Dedon, Peter C. ; Geacintov, Nicholas ; Shafirovich, Vladimir. / Photosensitized oxidative DNA damage : From hole injection to chemical product formation and strand cleavage. In: Journal of the American Chemical Society. 2007 ; Vol. 129, No. 30. pp. 9321-9332.
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