Cationic peptides containing tyrosine protect against radiation-induced oxidative DNA damage

Abstract

Purpose: To examine the effect of the amino acid tyrosine on oxidatively or direct-type damaged DNA damage when it is present in a DNA binding ligand.Materials and methods: We made use of tetralysine ligands to ensure binding to DNA and to condense the DNA, and simulated direct-type damage by using gamma irradiation in the presence of thiocyanate ions. These ligands contained an additional C terminal amino acid. Phenylalanine was used as a control for tyrosine. These ligands were used in conjuction with a plasmid substrate to quantify strand break yields. Base damage yields were estimated by measuring the strand break yield after incubation of the plasmid with the bacterial base excision repair enzyme formamidopyrimidine-DNA N-glycosylase (FPG).Results: When the condensing ligand contains an additional tyrosine or tryptophan residue, the plasmid is protected against the effects of a single electron oxidation, as assayed by sensitivity to a base excision repair enzyme. This protection is significantly greater in condensed plasmid where the amino acid residues are in close proximity to the DNA, and can be observed even when only a small fraction of the ligand contains tyrosine.Conclusions: Bound tyrosine residues located in close proximity to DNA are capable of reversing oxidative DNA damage far more efficiently than when present unbound in the bulk solution. This suggests that tyrosine residues in DNA binding proteins may participate in the repair of DNA that has been oxidatively damaged by ionizing radiation.