The Influence of Single, Tandem, and Clustered DNA Damage on the Electronic Properties of the Double Helix: A Theoretical Study

Abstract

<jats:p>Oxidatively generated damage to DNA frequently appears in the human genome as the effect of aerobic metabolism or as the result of exposure to exogenous oxidizing agents, such as ionization radiation. In this paper, the electronic properties of single, tandem, and clustered DNA damage in comparison with native ds-DNA are discussed as a comparative analysis for the first time. A single lesion—8-oxo-7,8-dihydro-2′-deoxyguanosine (Goxo), a tandem lesion—(5′S) and (5′R) 5′,8-cyclo-2′-deoxyadenosine (cdA), and the presence of both of them in one helix turn as clustered DNA damage were chosen and taken into consideration. The lowest vertical and adiabatic potential (VIP ~ 5.9 and AIP ~ 5.5 eV, respectively) were found for Goxo, independently of the discussed DNA lesion type and their distribution within the double helix. Moreover, the VIP and AIP were assigned for ds-trimers, ds- dimers and single base pairs isolated from parental ds-hexamers in their neutral and cationic forms. The above results were confirmed by the charge and spin density population, which revealed that Goxo can be considered as a cation radical point of destination independently of the DNA damage type (single, tandem, or clustered). Additionally, the different influences of cdA on the charge transfer rate were found and discussed in the context of tandem and clustered lesions. Because oligonucleotide lesions are effectively produced as a result of ionization factors, the presented data in this article might be valuable in developing a new scheme of anticancer radiotherapy efficiency.</jats:p>

FapydG in the Shadow of OXOdG—A Theoretical Study of Clustered DNA Lesions

“…The differences in charge and spin distribution between the non-equilibrated and equilibrated state of the vertical cation was less than 5% per the BPs mentioned. This finding is consistent with previous experimental and theoretical results [ 32 , 33 ]. It is important to note that no extra charge and spin was found within the Fapy G 2 ::C 4 moiety.…”

How (5′S) and (5′R) 5′,8-Cyclo-2′-Deoxypurines Affect Base Excision Repair of Clustered DNA Damage in Nuclear Extracts of xrs5 Cells? A Biochemical Study

“…That being the case, lesions are usually repaired by BER in a sequence and one at a time to avoid the risk of errors, strand breaks, and further mutations [ 9 ]. CdPus affect the geometry of the DNA helix in the 5′ direction from the lesion and inhibit the activity of the BER system [ 23 , 24 ]. It impacts the ability of particular repair enzymes to form complexes with DNA leading to a decline in repair capacity [ 10 , 25 , 26 ].…”

Recognition of a tandem lesion by DNA bacterial formamidopyrimidine glycosylases explored combining molecular dynamics and machine learning

“…The interaction of MDS-containing oligonucleotides with repair enzymes and in particular both E. Coli and human endonucleases [34] , [16] has been reported. The perturbations exerted by the secondary lesion on the protein/DNA contact regions, and the consequent decrease in its repair efficiency, as observed for some particular tandem lesions, have also been highlighted [16] , [35] , [36] , [37] , [38] . However, no analysis of the structural behavior of MutM in presence of tandem DNA lesions has been reported, despite the relevance that such lesions may assume in conditions of strong oxidative stress or ionizing radiations.…”