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How Clustered DNA Damage Can Change the Electronic Properties of ds-DNA—Differences between GAG, GA(OXO)G, and (OXO)GA(OXO)G

Every 24 h, roughly 3 × 10(17) 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...

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Detalles Bibliográficos
Autor principal: Karwowski, Boleslaw
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10046028/
https://www.ncbi.nlm.nih.gov/pubmed/36979452
http://dx.doi.org/10.3390/biom13030517
Descripción
Sumario:Every 24 h, roughly 3 × 10(17) 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 ((OXO)G) has been recognized as the most common lesion. In these studies, the influence of (OXO)G, as an isolated (oligo-(O)G) or clustered DNA lesion (oligo-(O)G(O)G), 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 (OXO)G constitutes the sink for migrated radical cations. However, in the case of oligo-(O)G(O)G containing a 5′-(OXO)GA(XOX)G-3′ sequence, the 3′-End (OXO)G becomes predisposed to electron-hole accumulation contrary to the undamaged GAG fragment. Moreover, it was found that the 5′-End (OXO)G present in an (OXO)GA(OXO)G 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.