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Understanding the details of DNA damage caused by high-energy particles or photons is complicated by the multitude of reactive species, arising from the ionization and dissociation of H2O, DNA, and protein. In this work, oligonucleotides (ODNs) are irradiated with a beam of low-energy electrons of 1.3 to 2.3 eV, which can only induce damage via the decay of shape resonances into various dissociative electron attachment channels. Using LC–MS/MS analysis, the major products are the release of nonmodified nucleobases (NB; Cyt ≫ Thy ∼ Ade > Gua). Additional damage includes 5,6-dihydropyrimidines (dHT > dHU) and eight nucleosides with modified sugar moieties consisting of 2′,3′- and 2′,5′-dideoxynucleosides (ddG > ddA ∼ ddC > ddT). The distribution of products is remarkably different in a 16-mer ODN compared to that observed previously with thymidylyl-(3′-5′)-thymidine. This difference is explained by electron delocalization occurring within a sufficiently long strand, the DEA theory of O’Malley, and recent time-dependent density functional theory calculations.

The presence of gold nanoparticles (AuNPs) greatly enhances the formation of DNA damage when exposed to therapeutic X-rays. Three types of DNA damage are assessed in irradiated DNA by enzymatic digestion coupled to liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The major type of damage is release of the four nonmodified nucleobases, with a bias toward the release of cytosine and thymine. The second most important pathway involves the formation of several common reduction and oxidation products of DNA. Lastly, eight unique modifications of the 2-deoxyribose moiety are formed, which includes the 2′,3′-and 2′,5′-dideoxynucleosides (ddNs) of the four canonical nucleosides. The yield of ddNs decreases in the following order: ddG > ddA > ddC > ddT. From the yield and distribution of products, most of the damage is considered to arise from the generation of Auger/low-energy electrons (LEEs) and their reaction with DNA.

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Closely located multiple abasic sites or clustered abasic sites are highly mutagenic and potentially cytotoxic.They have been found to be repair resistant in several in vitro studies. We studied the efficiency of the repair of clustered abasic sites by the APE1 enzyme in nucleosome core particles (NCPs). Sequences having genomic importance as the core sequence of TATA box and CpG islands were used to assemble the NCPs where the abasic clusters are located around the A/T or G/C rich 0.5 positioning site of the NCPs.The thermodynamics of the binding and repair of the A/T or G/C encased clustered abasic sites in the NCPs by APE1 enzyme are reported herein for the first time that was monitored by Isothermal Titration Calorimetry (ITC). The A/T encased clustered abasic sites in the NCP showed greater binding affinity with APE1 than the G/C counterpart. A/T encased abasic sites are also cleaved faster to generate double strand breaks by APE1 enzyme as compared to the CpG island sequence in the NCP, albeit at much slower rate than the linear model. Although, the overall reactivity of the abasic sites is appreciably reduced in the NCPs, distinct differences exist in the processing of the abasic sites that are flanked by A/T or G/C rich sequence. Our study suggests that both sequence effect and nucleosomal positioning are important determinants for the repair efficiency of clustered abasic sites in NCPs. 612 225 7383; Tel: +91 612 255 2057 † Electronic supplementary information (ESI) available. See