Nucleic Acids Research, Vol 27, Issue 19 3805-3810, Copyright © 1999 by Oxford University Press
JT Hwang, KA Tallman and MM Greenberg
The formal C1'-oxidation product, 2-deoxyribonolactone, is formed as a
result of DNA damage induced via a variety of agents, including gamma-
radiolysis and the enediyne antitumor antibiotics. This alkaline labile
lesion may also be an intermediate during DNA damage induced by copper-
phenanthroline. Oligo-nucleotides containing this lesion at a defined site
were formed via aerobic photolysis of oligonucleotides containing a
photolabile ketone, and were characterized by gel electrophoresis and
electrospray mass spectrometry (ESI-MS). Treatment of oligo-nucleotides
containing the lesion with secondary amines produces strand breaks
consisting of 3'-phosphate termini, and products which migrate more slowly
in polyacrylamide gels. MALDI-TOF mass spectrometry analysis indicates that
the slower moving products are formal adducts of the beta-elimination
product resulting from 2-deoxyribonolactone and one molecule of amine. The
addition of beta-mercapto-ethanol to the reaction mixture produces thiol
adducts as well. The stability of these adducts suggests that they cannot
be the labile species characterized by gel electrophoresis in
copper-phenanthroline-mediated strand scission. The characterization of
these adducts by mass spectrometry also provides, by analogy, affirmation
of proposals regarding the reactivity of nucleophiles with the
beta-elimination product of abasic sites. Finally, the effects of this
lesion and the various adducts on DNA repair enzymes are unknown, but their
facile generation from oligonucleotides containing a photolabile ketone
suggests that such issues could be addressed.
ARTICLES
The reactivity of the 2-deoxyribonolactone lesion in single-stranded DNA and its implication in reaction mechanisms of DNA damage and repair
Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA.
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