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Bulged Guanine is Uniquely Sensitive to Damage Caused by Visible‐Light Irradiation of Ethidium Bound to DNA: A Possible Role in Mutagenesis
Author(s) -
Henderson Paul T.,
Boone Edna,
Schuster Gary B.
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200201)85:1<135::aid-hlca135>3.0.co;2-h
Subject(s) - chemistry , guanine , ethidium bromide , dna , pyrimidine dimer , photochemistry , duplex (building) , cleavage (geology) , dna damage , stereochemistry , biophysics , biochemistry , nucleotide , geotechnical engineering , fracture (geology) , biology , engineering , gene
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 H 2 O, 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.