The interaction of ethidium bromide (= 3,8-diamino-5-ethyl-6-phenylphenanthridinium bromide; EB) with a series of duplex DNA oligomers having single-base bulges and single-base mis-pairs was investigated (Fig. 1). Physical and spectroscopic analysis reveals no definitive evidence for selective binding of EB at the bulge or mis-pair. However, irradiation of the bound EB with VIS light leads to lesions in the DNA selectively in the sequence having a bulged guanine. This reaction is attributed to the formation of an exciplex between the lowest excited singlet state of the EB and the bulged guanine. The exciplex is trapped by H2O, which initiates a sequence of reactions that lead to piperidine-requiring strand cleavage at this site. Significantly, the damaged bulged guanine is not recognized by E. coli formamidopyrimidine glycosylase (Fpg), which is part of a base-excision repair system for oxidative damage to DNA. Thus, DNA containing a bulged guanine and having a bound intercalator may be irreparably damaged by exposure to VIS light, even though normal duplex DNA is relatively inert under these conditions.
|Original language||English (US)|
|Number of pages||17|
|Journal||Helvetica Chimica Acta|
|State||Published - 2002|
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