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
Approximately 3 × 10<sup>17</sup> 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...
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MDPI AG
2020-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/9/2/424 |
| _version_ | 1797701140869021696 |
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| author | Boleslaw T. Karwowski |
| author_facet | Boleslaw T. Karwowski |
| author_sort | Boleslaw T. Karwowski |
| collection | DOAJ |
| description | Approximately 3 × 10<sup>17</sup> 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 - <sup>oxo</sup>dG). Here, the influence of cdA, “the simplest tandem lesion”, on the charge transfer through <i>ds</i>-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′<i>S</i>)- or (5′<i>R</i>)-cdA leads to a slowdown in the hole transfer by one order of magnitude between the neighboring dG→<sup>oxo</sup>dG in comparison to “native” <i>ds</i>-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, <sup>oxo</sup>dG: dA base pair prior to genetic information replication can finally result in GC → TA or AT→CG 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. |
| first_indexed | 2024-03-12T04:31:01Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T04:31:01Z |
| publishDate | 2020-02-01 |
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| series | Cells |
| spelling | doaj.art-a914bb59de9148fc9460b4f900abdd932023-09-03T10:05:03ZengMDPI AGCells2073-44092020-02-019242410.3390/cells9020424cells9020424Clustered 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 ApproachBoleslaw T. Karwowski0DNA Damage Laboratory of Food Science Department, Faculty of Pharmacy, Medical University of Lodz, ul. Muszynskiego 1, 90-151 Lodz, PolandApproximately 3 × 10<sup>17</sup> 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 - <sup>oxo</sup>dG). Here, the influence of cdA, “the simplest tandem lesion”, on the charge transfer through <i>ds</i>-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′<i>S</i>)- or (5′<i>R</i>)-cdA leads to a slowdown in the hole transfer by one order of magnitude between the neighboring dG→<sup>oxo</sup>dG in comparison to “native” <i>ds</i>-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, <sup>oxo</sup>dG: dA base pair prior to genetic information replication can finally result in GC → TA or AT→CG 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.https://www.mdpi.com/2073-4409/9/2/424clustered dna damage5′,8-cyclo-2′-deoxyadenosinescharge transferglycosylasesbase excision repairdft |
| spellingShingle | Boleslaw T. Karwowski 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 clustered dna damage 5′,8-cyclo-2′-deoxyadenosines charge transfer glycosylases base excision repair dft |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | clustered dna damage 5′,8-cyclo-2′-deoxyadenosines charge transfer glycosylases base excision repair dft |
| url | https://www.mdpi.com/2073-4409/9/2/424 |
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