Specific recognition of apurinic sites in DNA by a tryptophan-containing peptide.

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Abstract
Fluorescence spectroscopy was used to study the binding of lysyltryptophyl-.alpha.-lysine (Lys-Trp-Lys) to DNA modified by dimethyl sulfate before and after depurination and strand breakage. Quenching of tryptophan fluoresence increased upon association of the peptide with modified DNA as compared with native [Escherichia coli, Micrococcus luteus, Bacillus subtilis or calf thymus] DNA. This quenching is related to a preferential stacking of the indole ring with nucleic acid bases in damaged regions. Stacking increased in the following order: methylated DNA < DNA with strand breaks at apurinic sites .mchgt. apurinic DNA. For apurinic DNA, the overall association constant of Lys-Trp-Lys was increased by more than 2 orders of magnitude as compared to native DNA. Enhancement of the affinity of the tripeptide for an apurinic site requires the integrity of the phosphodiester bond. Single-strand cleavage at an apurinic site leads to a marked decrease of the association constant. The peptide Lys-Trp-Lys is able to recognize destabilized regions in the vicinity of a lesion and to discriminate between different configurations of the damaged region. These results are discussed with respect to the role that stacking interactions could play in the specificity of recognition of DNA alterations by enzymes involved in DNA repair mechanisms.

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