How Clustered DNA Damage Can Change the Electronic Properties of ds-DNA-Differences between GAG, GAG, and GAG.

Every 24 h, roughly 3 × 10 incidences of DNA damage are generated in the human body as a result of intra- or extra-cellular factors. The structure of the formed lesions is identical to that formed during radio- or chemotherapy. Increases in the clustered DNA damage (CDL) level during anticancer treatment have been observed compared to those found in untreated normal tissues. 7,8-dihydro-8-oxo-2'-deoxyguanosine (G) has been recognized as the most common lesion. In these studies, the influence of G, as an isolated (oligo-G) or clustered DNA lesion (oligo-GG), on charge transfer has been analyzed in comparison to native oligo-G. DNA lesion repair depends on the damage recognition step, probably via charge transfer. Here the electronic properties of short ds-oligonucleotides were calculated and analyzed at the M062x/6-31++G** level of theory in a non-equilibrated and equilibrated solvent state. The rate constant of hole and electron transfer according to Marcus' theory was also discussed. These studies elucidated that G constitutes the sink for migrated radical cations. However, in the case of oligo-GG containing a 5'-GAG-3' sequence, the 3'-End G becomes predisposed to electron-hole accumulation contrary to the undamaged GAG fragment. Moreover, it was found that the 5'-End G present in an GAG fragment adopts a higher adiabatic ionization potential than the 2'-deoxyguanosine of an undamaged analog if both ds-oligos are present in a cationic form. Because increases in CDL formation have been observed during radio- or chemotherapy, understanding their role in the above processes can be crucial for the efficiency and safety of medical cancer treatment.