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

Publisher: MDPI Country of Publication: Switzerland NLM ID: 101596414 Publication Model: Electronic Cited Medium: Internet ISSN: 2218-273X (Electronic) Linking ISSN: 2218273X NLM ISO Abbreviation: Biomolecules Subsets: MEDLINE

Original Publication: Basel, Switzerland : MDPI, 2011-

DNA Damage* ; DNA*/chemistry; Humans ; DNA Repair ; Deoxyguanosine/chemistry ; 8-Hydroxy-2'-Deoxyguanosine

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.

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Keywords: 7,8-dihydro-8-oxo-2′-deoxyguanosine; Base Excision Repair; DFT; electron hole and excess electron transfer; electronic properties; reactive oxygen species

9007-49-2 (DNA)
G9481N71RO (Deoxyguanosine)
88847-89-6 (8-Hydroxy-2'-Deoxyguanosine)

Date Created: 20230329 Date Completed: 20230330 Latest Revision: 20230331

20250114

PMC10046028

10.3390/biom13030517

36979452