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. 1981 Feb;78(2):926–930. doi: 10.1073/pnas.78.2.926

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

T Behmoaras, J J Toulme, C Helene
PMCID: PMC319917  PMID: 6940157

Abstract

We have used fluorescence spectroscopy 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 fluorescence increased upon association of the peptide with modified DNA as compared with native DNA. We have demonstrated that 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 less than DNA with strand breaks at apurinic sites much less than apurinic DNA. For apurinic DNA, the overall association constant of Lys-Trp-Lys was increased by more than two 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 therefore 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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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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