Protection of DNA against Direct Radiation Damage by Complex Formation with Positively Charged Polypeptides

Abstract

Radioprotection of DNA from direct-type radiation damage by histones has been studied in model systems using complexes of positively charged polypeptides (PCPs) with DNA. PCPs bind to DNA via ionic interactions mimicking the mode of DNA-histone binding. Direct radiation damage to DNA in films of DNA-PCP complexes was quantified as unaltered base release, which correlates closely with DNA strand breaks. All types of PCPs tested protected DNA from radiation, with the maximum radioprotection being approximately 2.5-fold compared with non-complexed DNA. Conformational changes of the DNA induced by PCPs or repair of free radical damage on the DNA sugar moiety by PCPs are considered the most feasible mechanisms of radioprotection of DNA. The degree of radioprotection of DNA by polylysine (PL) increased dramatically on going from pure DNA to a molar ratio of PL monomer:DNA nucleotide ~1:2, while a further increase in the PL:DNA ratio did not offer more radioprotection. This concentration dependence is in agreement with the model of PCP binding to DNA that assumes preferential binding of positively charged side groups to DNA phosphates in the minor groove, so that the maximum occupancy of all minor-groove PCP binding sites is at a molar ratio of PCP:DNA = 1:2.

Damage to amino acid–nucleotide pairs induced by 1 eV electrons

“…A similar dependence was observed for the total base release, which can be correlated with DNA strand breaks, from polypeptide-DNA films irradiated by X-rays. 13 Studies on the radioprotection of DNA from direct damage by polypeptides have shown that poly-L-lysine protected DNA by a factor of approximately 2.5, while poly-L-arginine protected by a factor of 1.8.…”

“…The studies on direct damage to complexes of positively charged polypeptides with DNA induced by X-rays showed that the degree of DNA radioprotection increases with a molar ratio of polypeptides. 13 These polypeptide-DNA complexes provide a better mimic of the cellular situation, where DNA is bonded to histones via ionic interactions. Moreover, recently it has been also shown that organic ions can prevent alterations in DNA induced by 10 eV electrons.…”

X-ray induced damage in DNA monitored by X-ray photoelectron spectroscopy

“…1,2 The first type is due to the attack of DNA by highly reactive radicals that are products of ionizations in the surrounding medium. However, the mobility of formed radicals is not significant and, additionally, the presence of radical scavengers in cells often protects the DNA molecule.…”

Heterochromatin: an epigenetic point of view in aging

“…Cellular genomes are continuously damaged by reactive oxygen species through various processes 18 . An in vitro study showed that the binding of histones to DNA and their organization into higher-order chromatin structures dramatically protects DNA against hydroxyl radicalinduced DNA strand breaks as well as some types of radiation-induced damage [19][20][21] . This suggests that heterochromatin contributes to cellular defense against the induction of oxidative DNA damage 22,23 .…”