Paradoxical hotspots for guanine oxidation by a chemical mediator of inflammation.
Guanine in DNA is a major oxidation target owing to its low ionization potential (IP), and there is often an inverse correlation between damage frequency and sequence-dependent variation in guanine IP. We report that the biological oxidant nitrosoperoxycarbonate (ONOOCO2(-)) paradoxically selects guanines with the highest IP in GC-containing contexts. Along with sequence-dependent variation in damage chemistry, this behavior points to factors other than charge migration as determinants of genomic DNA oxidation.
Margolin
Yelena
Y
Biological Engineering Division, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Cloutier
Jean-Francois
JF
Shafirovich
Vladimir
V
Geacintov
Nicholas E
NE
Dedon
Peter C
PC
D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D006147:Guanine / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000737:chemistry / Q000494:pharmacology*; D007477:Ions / Q000737:chemistry; D016877:Oxidants / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D010777:Photochemistry; D012256:Riboflavin / Q000737:chemistry / Q000494:pharmacology
D018836:Inflammation Mediators; D007477:Ions; D016877:Oxidants; D006147:Guanine; D004247:DNA; D012256:Riboflavin