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Clustered DNA Damage: Electronic Properties and Their Influence on Charge Transfer. 7,8-Dihydro-8-Oxo-2′-Deoxyguaosine Versus 5′,8-Cyclo-2′-Deoxyadenosines: A Theoretical Approach

DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, Poland
Cells 2020, 9(2), 424; https://doi.org/10.3390/cells9020424
Received: 10 January 2020 / Revised: 2 February 2020 / Accepted: 11 February 2020 / Published: 12 February 2020
Approximately 3 × 1017 DNA damage events take place per hour in the human body. Within clustered DNA lesions, they pose a serious problem for repair proteins, especially for iron–sulfur glycosylases (MutyH), which can recognize them by the electron-transfer process. It has been found that the presence of both 5′,8-cyclo-2′-deoxyadenosine (cdA) diastereomers in the ds-DNA structure, as part of a clustered lesion, can influence vertical radical cation distribution within the proximal part of the double helix, i.e., d[~oxoGcAoxoG~] (7,8-dihydro-8-oxo-2′-deoxyguaosine - oxodG). Here, the influence of cdA, “the simplest tandem lesion”, on the charge transfer through ds-DNA was taken into theoretical consideration at the M062x/6-31+G** level of theory in the aqueous phase. It was shown that the presence of (5′S)- or (5′R)-cdA leads to a slowdown in the hole transfer by one order of magnitude between the neighboring dGoxodG in comparison to “native” ds-DNA. Therefore, it can be concluded that such clustered lesions can lead to defective damage recognition with a subsequent slowing down of the DNA repair process, giving rise to an increase in mutations. As a result, the unrepaired, oxodG: dA base pair prior to genetic information replication can finally result in GC TA or ATCG transversion. This type of mutation is commonly observed in human cancer cells. Moreover, because local multiple damage sites (LMSD) are effectively produced as a result of ionization factors, the presented data in this article might be useful in developing a new scheme of radiotherapy treatment against the background of DNA repair efficiency.
Keywords: Clustered DNA damage; 5′,8-cyclo-2′-deoxyadenosines; Charge transfer; Glycosylases; Base Excision Repair; DFT Clustered DNA damage; 5′,8-cyclo-2′-deoxyadenosines; Charge transfer; Glycosylases; Base Excision Repair; DFT
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    Doi: 10.5281/zenodo.3604312
    Link: https://zenodo.org/deposit/3604312
    Description: Supplementary Materials of article entitled: Clustered DNA damage: electronic properties and their influence on charge transfer. 7,8-dihydro-8-oxo-2'-deoxyguaosine versus 5',8-cyclo-2'-deoxyadenosines: a theoretical approach.
MDPI and ACS Style

Karwowski, B.T. Clustered DNA Damage: Electronic Properties and Their Influence on Charge Transfer. 7,8-Dihydro-8-Oxo-2′-Deoxyguaosine Versus 5′,8-Cyclo-2′-Deoxyadenosines: A Theoretical Approach. Cells 2020, 9, 424.

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