Formation of 5′,8-cyclo-2′-deoxyadenosine in single strand DNA. Theoretical quantum mechanics study

Karwowski, Bolesław T.

doi:10.1039/b920373g

Cited by 9 publications

(9 citation statements)

References 36 publications

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“…Both types of lesions taken into consideration can be formed by hydroxyl radical activity. However, the dG oxo by •OH addition to the C8 moiety of dG while the 5′ R and 5′ S diastereomers of 5′,8-cyclo-2′deoxyadenosine can occur in ds -DNA as a result of a two-step cyclization reaction induced by hydrogen atom abstraction from the C5′ position by a hydrogen radical [ 65 ]. These unusual tandem lesions can lead to different local spatial geometry changes in the double helix, next to their place of formation [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

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

Karwowski

2020

Molecules

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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.

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Section: Discussionmentioning

confidence: 99%

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

Karwowski

2020

Molecules

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“…However, the frequency of cdA depends on the source/tissue taken into consideration, as well as the techniques used for detection [41,42]. The cdA is the product of C5'-C8 cyclization initiated by one of the C5' proton • OH abstractions [43]. It should be pointed out here that cdA is the simplest tandem lesion.…”

Section: Introductionmentioning

confidence: 99%

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

Karwowski

2020

Cells

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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 dG→oxodG 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 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.

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“…28–30 Both the R - and S -diastereomers of the 8,5′-cA ribonucleoside have been crystallized. 31,32 Both exhibited the anti conformation about the glycosyl bond with χ O4′-C1′-N9-C8 = 29.8° or 27.4°, respectively.…”

Section: Introductionmentioning

confidence: 99%

Structure of (5′S)-8,5′-Cyclo-2′-deoxyguanosine in DNA

et al. 2011

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Diastereomeric 8,5′-cyclopurine 2′-deoxynucleosides, containing a covalent bond between the deoxyribose and the purine base, represent an important class of DNA damage induced by ionizing radiation. The 8,5′-cyclo-2′-deoxyguanosine lesion (cdG) has been recently reported to be a strong block of replication and highly mutagenic in Escherichia coli. The 8,5′-cyclopurine-2′-deoxyriboses are suspected to play a role in the etiology of neurodegeneration in xeroderma pigmentosum patients. These lesions cannot be repaired by base excision repair, but they are substrates for nucleotide excision repair. The structure of an oligodeoxynucleotide duplex containing a site-specific S-cdG lesion placed opposite dC in the complementary strand was obtained by molecular dynamics calculations restrained by distance and dihedral angle restraints obtained from NMR spectroscopy. The S-cdG deoxyribose exhibited the O4′-exo (west) pseudorotation. Significant perturbations were observed for the β, γ, and χ torsion angles of the S-cdG nucleoside. Watson-Crick base pairing was conserved at the S-cdG•dC pair. However, the O4′-exo pseudorotation of the S-cdG deoxyribose perturbed the helical twist and base pair stacking at the lesion site and the 5′-neighbor dC•dG base pair. Thermodynamic destabilization of the duplex measured by UV melting experiments correlated with base stacking and structural perturbations involving the modified S-cdG•dC and 3′- neighbor dT•dA base pairs. These perturbations may be responsible for both the genotoxicity of this lesion and its ability to be recognized by nucleotide excision repair.

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Formation of 5′,8-cyclo-2′-deoxyadenosine in single strand DNA. Theoretical quantum mechanics study

Cited by 9 publications

References 36 publications

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

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

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

Structure of (5′S)-8,5′-Cyclo-2′-deoxyguanosine in DNA

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