Requirement of transcription-coupled nucleotide excision repair for the removal of a specific type of oxidatively induced DNA damage.

Accumulation of DNA damage resulting from reactive oxygen species was proposed to cause neurological and degenerative disease in patients, deficient in nucleotide excision repair (NER) or its transcription-coupled subpathway (TC-NER). Here, we assessed the requirement of TC-NER for the repair of specific types of oxidatively generated DNA modifications. We incorporated synthetic 5',8-cyclo-2'-deoxypurine nucleotides (cyclo-dA, cyclo-dG) and thymine glycol (Tg) into an EGFP reporter gene to measure transcription-blocking potentials of these modifications in human cells. Using null mutants, we further identified the relevant DNA repair components by a host cell reactivation approach. The results indicated that NTHL1-initiated base excision repair is by far the most efficient pathway for Tg. Moreover, Tg was efficiently bypassed during transcription, which effectively rules out TC-NER as an alternative repair mechanism. In a sharp contrast, both cyclopurine lesions robustly blocked transcription and were repaired by NER, wherein the specific TC-NER components CSB/ERCC6 and CSA/ERCC8 were as essential as XPA. Instead, repair of classical NER substrates, cyclobutane pyrimidine dimer and N-(deoxyguanosin-8-yl)-2-acetylaminofluorene, occurred even when TC-NER was disrupted. The strict requirement of TC-NER highlights cyclo-dA and cyclo-dG as candidate damage types, accountable for cytotoxic and degenerative responses in individuals affected by genetic defects in this pathway.

The Antioxidant Potential of Commercial Manuka Honey from New Zealand-Biochemical and Cellular Studies.

Manuka honey (MH) is considered a superfood mainly because of its various health-promoting properties, including its anti-cancer, anti-inflammatory, and clinically proven antibacterial properties. A unique feature of Manuka honey is the high content of methylglyoxal, which has antibacterial potential. Additionally, it contains bioactive and antioxidant substances such as polyphenols that contribute to its protective effects against oxidative stress. In this study, commercially available Manuka honey was tested for its total polyphenol content and DPPH radical scavenging ability. It was then tested in vitro on human fibroblast cells exposed to UV radiation to assess its potential to protect cells against oxidative stress. The results showed that the honey itself significantly interfered with cell metabolism, and its presence only slightly alleviated the effects of UV exposure. This study also suggested that the MGO content has a minor impact on reducing oxidative stress in UV-irradiated cells and efficiency in scavenging the DPPH radical.

The Influence of Oxidized Imino-Allantoin in the Presence of OXOG on Double Helix Charge Transfer: A Theoretical Approach.

The genome is continuously exposed to a variety of harmful factors that result in a significant amount of DNA damage. This article examines the influence of a multi-damage site containing oxidized imino-allantoin (OXIa) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[A1OXIa2A3OXOG4A5]*d[T5C4T3C2T1] structure was obtained at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the condensed phase, with the energies obtained at the M06-2X/6-31++G** level. The non-equilibrated and equilibrated solvent-solute interactions were also considered. Theoretical studies reveal that the radical cation prefers to settle on the OXOG moiety, irrespective of the presence of OXIa in a ds-oligo. The lowest vertical and adiabatic ionization potential values were found for the OXOG:::C base pair (5.94 and 5.52 [eV], respectively). Conversely, the highest vertical and adiabatic electron affinity was assigned for OXIaC as follows: 3.15 and 3.49 [eV]. The charge transfers were analyzed according to Marcus' theory. The highest value of charge transfer rate constant for hole and excess electron migration was found for the process towards the OXOGC moiety. Surprisingly, the values obtained for the driving force and activation energy of electro-transfer towards OXIa2C4 located this process in the Marcus inverted region, which is thermodynamically unfavorable. Therefore, the presence of OXIa can slow down the recognition and removal processes of other DNA lesions. However, with regard to anticancer therapy (radio/chemo), the presence of OXIa in the structure of clustered DNA damage can result in improved cancer treatment outcomes.

The Effect of 8,5'-Cyclo 2'-deoxyadenosine on the Activity of 10-23 DNAzyme: Experimental and Theoretical Study.

The in vivo effectiveness of DNAzymes 10-23 (Dz10-23) is limited due to the low concentration of divalent cations. Modifications of the catalytic loop are being sought to increase the activity of Dz10-23 in physiological conditions. We investigated the effect of 5'S or 5'R 5',8-cyclo-2'deoxyadenosine (cdA) on the activity of Dz10-23. The activity of Dz10-23 was measured in a cleavage assay using radiolabeled RNA. The Density Functional Tight Binding methodology with the self-consistent redistribution of Mulliken charge modification was used to explain different activities of DNAzymes. The substitution of 2'-deoxyadenosine with cdA in the catalytic loop decreased the activity of DNAzymes. Inhibition was dependent on the position of cdA and its absolute configuration. The order of activity of DNAzymes was as follows: wt-Dz > ScdA5-Dz ≈ RcdA15-Dz ≈ ScdA15-Dz > RcdA5-Dz. Theoretical studies revealed that the distance between phosphate groups at position 5 in RcdA5-Dz was significantly increased compared to wt-Dz, while the distance between O4 of dT4 and nonbonding oxygen of PO2 attached to 3'O of dG2 was much shorter. The strong inhibitory effect of RcdA5 may result from hampering the flexibility of the catalytic loop (increased rigidity), which is required for the proper positioning of Me2+ and optimal activity.

The Influence of 2'-Deoxyguanosine Lesions on the Electronic Properties of OXOG:::C Base Pairs in Ds-DNA: A Comparative Analysis of Theoretical Studies.

DNA is continuously exposed to a variety of harmful factors, which, on the one hand, can force undesirable processes such as ageing, carcinogenesis and mutagenesis, while on the other hand, can accelerate evolutionary changes. Of all the canonical nucleosides, 2'-deoxyguanosine (dG) exhibits the lowest ionization potential, making it particularly prone to the one-electron oxidizing process. The most abundant type of nucleobase damage is constituted by 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG), with an oxidation potential that is 0.56 V lower than that of canonical dG. All this has led to OXOdG, as an isolated lesion, being perceived as a sink for radical cations in the genome. In this paper, a comparative analysis of the electronic properties of an OXOGC base pair within the context of a clustered DNA lesion (CDL) has been conducted. It is based on previous DFT studies that were carried out at the M06-2x/6-31++G** level of theory in non-equilibrated and equilibrated condensed phases. The results of the comparative analysis presented here reveal the following: (A) The ionization potentials of OXOG4C2 were largely unaffected by a second lesion. (B) The positive charge and spin were found predominantly on the OXOG4C2 moiety. (C) The electron-hole transfers A3T3→G4C2 and G4C2←A5T1 were found in the Marcus inverted region and were resistant to the presence of a second DNA lesion in close proximity. It can therefore be reasonably postulated that OXOGC becomes the sink for a radical cation migrating through the double helix, irrespective of the presence of other 2'-deoxyguanosine lesions in the CDL structure.

The Influence of Clustered DNA Damage Containing Iz/Oz and OXOdG on the Charge Transfer through the Double Helix: A Theoretical Study.

The genome-the source of life and platform of evolution-is continuously exposed to harmful factors, both extra- and intra-cellular. Their activity causes different types of DNA damage, with approximately 80 different types of lesions having been identified so far. In this paper, the influence of a clustered DNA damage site containing imidazolone (Iz) or oxazolone (Oz) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (OXOdG) on the charge transfer through the double helix as well as their electronic properties were investigated. To this end, the structures of oligo-Iz, d[A1Iz2A3OXOG4A5]*d[T5C4T3C2T1], and oligo-Oz, d[A1Oz2A3OXOG4A5]*d[T5C4T3C2T1], were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using the ONIOM methodology; all the discussed energies were obtained at the M06-2X/6-31++G** level of theory. The non-equilibrated and equilibrated solvent-solute interactions were taken into consideration. The following results were found: (A) In all the discussed cases, OXOdG showed a higher predisposition to radical cation formation, and B) the excess electron migration toward Iz and Oz was preferred. However, in the case of oligo-Oz, the electron transfer from Oz2 to complementary C4 was noted during vertical to adiabatic anion relaxation, while for oligo-Iz, it was settled exclusively on the Iz2 moiety. The above was reflected in the charge transfer rate constant, vertical/adiabatic ionization potential, and electron affinity energy values, as well as the charge and spin distribution. It can be postulated that imidazolone moiety formation within the CDL ds-oligo structure and its conversion to oxazolone can significantly influence the charge migration process, depending on the C2 carbon hybridization sp2 or sp3. The above can confuse the single DNA damage recognition and removal processes, cause an increase in mutagenesis, and harm the effectiveness of anticancer therapy.

The Influence of Spirodi(Iminohydantoin) on Charge Transfer through ds-DNA Containing 8-OXO-dG: A Theoretical Approach.

Genetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 104 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (OXOG) is one of the most abundant and can undergo further transformations towards spirodi(iminohydantoin) (Sp). Sp is highly mutagenic in comparison to its precursor if not repaired. In this paper, the influence of both Sp diastereomers 4R and 4S as well as their anti and syn conformers on charge transfer through the double helix was taken into theoretical consideration. In addition, the electronic properties of four modelled double-stranded oligonucleotides (ds-oligos) were also discussed, i.e., d[A1Sp2A3oxoG4A5] * [T5C4T3C2T1]. Throughout the study, the M06-2X/6-31++G** level theory was used. Solvent-solute non-equilibrated and equilibrated interactions were also considered. The subsequent results elucidated that the 7,8-dihydro-8-oxo-guanosine:cytidine (OXOGC) base pair is the settled point of a migrated radical cation in each of the discussed cases, due to its low adiabatic ionization potential, i.e., ~5.55 [eV]. The opposite was noted for excess electron transfer through ds-oligos containing anti (R)-Sp or anti (S)-Sp. The radical anion was found on the OXOGC moiety, whereas in the presence of syn (S)-Sp or syn (R)-Sp, an excess electron was found on the distal A1T5 or A5T1 base pair, respectively. Furthermore, a spatial geometry analysis of the discussed ds-oligos revealed that the presence of syn (R)-Sp in the ds-oligo caused only a slight deformation to the double helix, while syn (S)-Sp formed an almost ideal base pair with a complementary dC. The above results are in strong agreement with the final charge transfer rate constant, as calculated according to Marcus' theory. In conclusion, DNA damage such as spirodi(iminohydantoin), especially when becoming part of clustered DNA damage, can affect the effectiveness of other lesion recognition and repair processes. This can lead to the acceleration of undesired and deleterious processes such as carcinogenesis or aging. However, in terms of anticancer radio-/chemo- or combined therapy, the slowing down of the repair machinery can result in increased effectiveness. With this in mind, the influence of clustered damage on charge transfer and its subsequent effect on single-damage recognition by glycosylases justifies future investigation.

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

Genetic information, irrespective of cell type (normal or cancerous), is exposed to a range of harmful factors, which can lead to more than 80 different types of DNA damage. Of these, oxoG and FapyG have been identified as the most abundant in normoxic and hypoxic conditions, respectively. This article considers d[AFapyGAOXOGA]*[TCTCT] (oligo-FapyG) with clustered DNA lesions (CDLs) containing both the above types of damage at the M06-2x/6-31++G** level of theory in the condensed phase. Furthermore, the electronic properties of oligo-FapyG were analysed in both equilibrated and non-equilibrated solvation-solute interaction modes. The vertical/adiabatic ionization potential (VIP, AIP) and electron affinity (VEA, AEA) of the investigated ds-oligo were found as follows in [eV]: 5.87/5.39 and -1.41/-2.09, respectively. The optimization of the four ds-DNA spatial geometries revealed that the transFapydG was energetically privileged. Additionally, CDLs were found to have little influence on the ds-oligo structure. Furthermore, for the FapyGC base-pair isolated from the discussed ds-oligo, the ionization potential and electron affinity values were higher than those assigned to OXOGC. Finally, a comparison of the influence of FapyGC and OXOGC on charge transfer revealed that, in contrast to the OXOGC base-pair, which, as expected, acted as a radical cation/anion sink in the oligo-FapyG structure, FapyGC did not significantly affect charge transfer (electron-hole and excess-electron). The results presented below indicate that 7,8-dihydro-8-oxo-2'-deoxyguanosine plays a significant role in charge transfer through ds-DNA containing CDL and indirectly has an influence on the DNA lesion recognition and repair process. In contrast, the electronic properties obtained for 2,6-diamino-4-hydroxy-5-foramido-2'deoxypyrimidine were found to be too weak to compete with OXOG to influence charge transfer through the discussed ds-DNA containing CDL. Because increases in multi-damage site formation are observed during radio- or chemotherapy, understanding their role in the above processes can be crucial for the efficiency and safety of medical cancer treatment.

The 2Ih and OXOG Proximity Consequences on Charge Transfer through ds-DNA: Theoretical Studies of Clustered DNA Damage.

Genetic information is continuously exposed to harmful factors, both intra- and extracellular. Their activity can lead to the formation of different types of DNA damage. Clustered lesions (CDL) are problematic for DNA repair systems. In this study, the short ds-oligos with a CDL containing (R) or (S) 2Ih and OXOG in their structure were chosen as the most frequent in vitro lesions. In the condensed phase, the spatial structure was optimized at the M062x/D95**:M026x/sto-3G level of theory, while the electronic properties were optimized at the M062x/6-31++G** level. The influence of equilibrated and non-equilibrated solvent-solute interactions was then discussed. It was found that the presence of (R)2Ih in the ds-oligo structure causes a greater increase in structure sensitivity towards charge adoption than (S)2Ih, while OXOG shows high stability. Moreover, the analysis of charge and spin distribution reveals the different effects of 2Ih diastereomers. Additionally, the adiabatic ionization potential was found as follows for (R)-2Ih and (S)-2Ih in eV: 7.02 and 6.94. This was in good agreement with the AIP of the investigated ds-oligos. It was found that the presence of (R)-2Ih has a negative influence on excess electron migration through ds-DNA. Finally, according to the Marcus theory, the charge transfer constant was calculated. The results presented in the article show that both diastereomers of 5-carboxamido-5-formamido-2-iminohydantoin should play a significant role in the CDL recognition process via electron transfer. Moreover, it should be pointed out that even though the cellular level of (R and S)-2Ih has been obscured, their mutagenic potential should be at the same level as other similar guanine lesions found in different cancer cells.

(5'S) 5',8-Cyclo-2'-Deoxyadenosine Cannot Stop BER. Clustered DNA Lesion Studies.

As a result of external and endocellular physical-chemical factors, every day approximately ~105 DNA lesions might be formed in each human cell. During evolution, living organisms have developed numerous repair systems, of which Base Excision Repair (BER) is the most common. 5',8-cyclo-2'-deoxyadenosine (cdA) is a tandem lesion that is removed by the Nucleotide Excision Repair (NER) mechanism. Previously, it was assumed that BER machinery was not able to remove (5'S)cdA from the genome. In this study; however, it has been demonstrated that, if (5'S)cdA is a part of a single-stranded clustered DNA lesion, it can be removed from ds-DNA by BER. The above is theoretically possible in two cases: (A) When, during repair, clustered lesions form Okazaki-like fragments; or (B) when the (5'S)cdA moiety is located in the oligonucleotide strand on the 3'-end side of the adjacent DNA damage site, but not when it appears at the opposite 5'-end side. To explain this phenomenon, pure enzymes involved in BER were used (polymerase ß (Polß), a Proliferating Cell Nuclear Antigen (PCNA), and the X-Ray Repair Cross-Complementing Protein 1 (XRCC1)), as well as the Nuclear Extract (NE) from xrs5 cells. It has been found that Polß can effectively elongate the primer strand in the presence of XRCC1 or PCNA. Moreover, supplementation of the NE from xrs5 cells with Polß (artificial Polß overexpression) forced oligonucleotide repair via BER in all the discussed cases.

The Influence of 5',8-Cyclo-2'-deoxypurines on the Mitochondrial Repair of Clustered DNA Damage in Xrs5 Cells: The Preliminary Study.

The 5',8-cyclo-2'-deoxypurines (cdPus) affect the DNA structure. When these bulky structures are a part of clustered DNA lesions (CDL), they affect the repair of the other lesions within the cluster. Mitochondria are crucial for cell survival and have their own genome, hence, are highly interesting in the context of CDL repair. However, no studies are exploring this topic. Here, the initial stages of mitochondrial base excision repair (mtBER) were considered-the strand incision and elongation. The repair of a single lesion (apurinic site (AP site)) accompanying the cdPu within the double-stranded CDL has been investigated for the first time. The type of cdPu, its diastereomeric form, and the interlesion distance were taken into consideration. For these studies, the established experimental model of short oligonucleotides (containing AP sites located ≤7 base pairs to the cdPu in both directions) and mitochondrial extracts of the xrs5 cells were used. The obtained results have shown that the presence of cdPus influenced the processing of an AP site within the CDL. Levels of strand incision and elongation were higher for oligos containing RcdA and ScdG than for those with ScdA and RcdG. Investigated stages of mtBER were more efficient for DNA containing AP sites located on 5'-end side of cdPu than on its 3'-end side. In conclusion, the presence of cdPus in mtDNA structure may affect mtBER (processing the second mutagenic lesion within the CDL). As impaired repair processes may lead to serious biological consequences, further studies concerning the mitochondrial repair of CDL are highly demanded.

When UDG and hAPE1 Meet Cyclopurines. How (5'R) and (5'S) 5',8-Cyclo-2'-deoxyadenosine and 5',8-Cyclo-2'-deoxyguanosine Affect UDG and hAPE1 Activity?

Ionizing radiation is a factor that seriously damages cellular mechanisms/macromolecules, e.g., by inducing damage in the human genome, such as 5',8-cyclo-2'-deoxypurines (cdPus). CdPus may become a component of clustered DNA lesions (CDL), which are notably unfavorable for the base excision repair system (BER). In this study, the influence of 5'S and 5'R diastereomers of 5',8-cyclo-2'-deoxyadenosine (cdA) and 5',8-cyclo-2'-deoxyguanosine (cdG) on the uracil-DNA glycosylase (UDG) and human AP site endonuclease 1 (hAPE1) activity has been taken under consideration. Synthetic oligonucleotides containing 2'-deoxyuridine (dU) and cdPu were used as a model of single-stranded CDL. The activity of the UDG and hAPE1 enzymes decreased in the presence of RcdG compared to ScdG. Contrary to the above, ScdA reduced enzyme activity more than RcdA. The presented results show the influence of cdPus lesions located within CDL on the activity of the initial stages of BER dependently on their position toward dU. Numerous studies have shown the biological importance of cdPus (e.g., as a risk of carcinogenesis). Due to that, it is important to understand how to recognize and eliminate this type of DNA damage from the genome.

The Influence of 5'R and 5'S cdA and cdG on the Activity of BsmAI and SspI Restriction Enzymes.

Restriction endonucleases (REs) are intra-bacterial scissors that are considered tools in the fight against foreign genetic material. SspI and BsmAI, examined in this study, cleave dsDNA at their site of recognition or within a short distance of it. Both enzymes are representatives of type II REs, which have played an extremely important role in research on the genetics of organisms and molecular biology. Therefore, the study of agents affecting their activity has become highly important. Ionizing radiation may damage basic cellular mechanisms by inducing lesions in the genome, with 5',8-cyclo-2'-deoxypurines (cdPus) as a model example. Since cdPus may become components of clustered DNA lesions (CDLs), which are unfavorable for DNA repair pathways, their impact on other cellular mechanisms is worthy of attention. This study investigated the influence of cdPus on the elements of the bacterial restriction-modification system. In this study, it was shown that cdPus present in DNA affect the activity of REs. SspI was blocked by any cdPu lesion present at the enzyme's recognition site. When lesions were placed near the recognition sequence, the SspI was inhibited up to 46%. Moreover, (5'S)-5',8-cyclo-2'-deoxyadenosine (ScdA) present in the oligonucleotide sequence lowered BsmAI activity more than (5'R)-5',8-cyclo-2'-deoxyadenosine (RcdA). Interestingly, in the case of 5',8-cyclo-2'-deoxyguanosine (cdG), both 5'S and 5'R diastereomers inhibited BsmAI activity (up to 55% more than cdA). The inhibition was weaker when cdG was present at the recognition site rather than the cleavage site.

The role of AMPK in metabolism and its influence on DNA damage repair.

One of the most complex health disproportions in the human body is the metabolic syndrome (MetS). It can result in serious health consequences such as type 2 diabetes mellitus, atherosclerosis or insulin resistance. The center of energy regulation in human is AMP-activated protein kinase (AMPK), which modulates cells' metabolic pathways and protects them against negative effects of metabolic stress, e.g. reactive oxygen species. Moreover, recent studies show the relationship between the AMPK activity and the regulation of DNA damage repair such as base excision repair (BER) system, which is presented in relation to the influence of MetS on human genome. Hence, AMPK is studied not only in the field of counteracting MetS but also prevention of genetic alterations and cancer development. Through understanding AMPK pathways and its role in cells with damaged DNA it might be possible to improve cell's repair processes and develop new therapies. This review presents AMPK role in eukaryotic cells and focuses on the relationship between AMPK activity and the regulation of BER system through its main component-8-oxoguanine glycosylase (OGG1).

Review: immunoassays in DNA damage and instability detection.

The review includes information on the current state of knowledge of immunometric methods with emphasis on the possibility of deoxyribonucleic acid (DNA) damage detection. Beginning with basic immunoassay enzyme-linked immunosorbent assay (ELISA), this review describes methods such as tyramide signal amplification (TSA), enhanced polymer one-step staining (EPOS), and time resolved amplified cryptate emission (TRACE) as improvements of ELISA's developed over time to obtain more accurate results. In the second part of the review, surface plasmon resonance (SPR) and quantum dots (QDs) are presented as the newest outlooks in the context of immunoanalysis of biological material and molecular studies. The aim of this review is to briefly present immunoassays with emphasis on DNA damage detection; therefore, the types of methods are listed and described, types of signal indicators, basic definitions such as antigen and antibody are given. Every method is considered with an exemplary application focusing on DNA studies, DNA damage and instability detection.

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

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.

The Electronic Property Differences between dA::dG and dA::dGoxo. A Theoretical Approach.

The dA::dGoxo pair appearing in nucleic ds-DNA can lead to a mutation in the genetic information. Depending on the dGoxo source, an AT→GC and GC→AC transversion might be observed. As a result, glycosylases are developed during the evolution, i.e., OGG1 and MutY. While the former effectively removes Goxo from the genome, the second one removes adenine from the dA::dGoxo and dA:dG pair. However, dA::dGoxo is recognized by MutY as ~6-10 times faster than dA:dG. In this article, the structural and electronic properties of simple nucleoside pairs dA:dG, dC:::dGoxo, dC:::dG, dA::dGoxo in the aqueous phase have been taken into theoretical consideration. The influence of solvent relaxation on the above is also discussed. It can be concluded that the dA::dGoxo nucleoside pair shows a lower ionization potential and higher electron affinity than the dA:dG pair in both a vertical and adiabatic mode. Therefore, it could be predicted, under electronic properties, that the electron ejected, for instance by a MutY 4[Fe-S]2+ cluster, is predisposed to trapping by the ds-DNA part containing the dA::dGoxo pair rather than by dA::dG.

The Similarities between Human Mitochondria and Bacteria in the Context of Structure, Genome, and Base Excision Repair System.

Mitochondria emerged from bacterial ancestors during endosymbiosis and are crucial for cellular processes such as energy production and homeostasis, stress responses, cell survival, and more. They are the site of aerobic respiration and adenosine triphosphate (ATP) production in eukaryotes. However, oxidative phosphorylation (OXPHOS) is also the source of reactive oxygen species (ROS), which are both important and dangerous for the cell. Human mitochondria contain mitochondrial DNA (mtDNA), and its integrity may be endangered by the action of ROS. Fortunately, human mitochondria have repair mechanisms that allow protecting mtDNA and repairing lesions that may contribute to the occurrence of mutations. Mutagenesis of the mitochondrial genome may manifest in the form of pathological states such as mitochondrial, neurodegenerative, and/or cardiovascular diseases, premature aging, and cancer. The review describes the mitochondrial structure, genome, and the main mitochondrial repair mechanism (base excision repair (BER)) of oxidative lesions in the context of common features between human mitochondria and bacteria. The authors present a holistic view of the similarities of mitochondria and bacteria to show that bacteria may be an interesting experimental model for studying mitochondrial diseases, especially those where the mechanism of DNA repair is impaired.

8-Oxo-7,8-Dihydro-2'-Deoxyguanosine (8-oxodG) and 8-Hydroxy-2'-Deoxyguanosine (8-OHdG) as a Potential Biomarker for Gestational Diabetes Mellitus (GDM) Development.

The growing clinical and epidemiological significance of gestational diabetes mellitus results from its constantly increasing worldwide prevalence, obesity, and overall unhealthy lifestyle among women of childbearing age. Oxidative stress seems to be the most important predictor of gestational diabetes mellitus development. Disturbances in the cell caused by oxidative stress lead to different changes in biomolecules, including DNA. The nucleobase which is most susceptible to oxidative stress is guanine. Its damage results in two main modifications: 8-hydroxy-2'-deoxyguanosineor 8-oxo-7,8-dihydro-2'-deoxyguanosine. Their significant level can indicate pathological processes during pregnancy, like gestational diabetes mellitus and probably, type 2 diabetes mellitus after pregnancy. This review provides an overview of current knowledge on the use of 8-hydroxy-2'-deoxyguanosineand/or 8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker in gestational diabetes mellitus and allows us to understand the mechanism of 8-hydroxy-2'-deoxyguanosineand/or 8-oxo-7,8-dihydro-2'-deoxyguanosine generation during this disease.

8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a Cause of Autoimmune Thyroid Diseases (AITD) During Pregnancy?

The thyroid is not necessary to sustain life. However, thyroid hormones (TH) strongly affect the human body. Functioning of the thyroid gland affects the reproductive capabilities of women and men, as well as fertilization and maintaining a pregnancy. For the synthesis of TH, hydrogen peroxide (H2O2) is necessary. From the chemical point of view, TH is a reactive oxygen species (ROS) and serves as an oxidative stress (OS) promoter. H2O2 concentration in the thyroid gland is much higher than in other tissues. Therefore, the thyroid is highly exposed to OS. 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) are DNA lesions resulting from ROS action onto guanine moiety. Due to their abundance, they are recognized as biomarkers of OS. As thyroid function is correlated with the level of OS, 8-oxodG and 8-OHdG has been taken under consideration. Studies correlate the oxidative DNA damage with various thyroid diseases (TD) such as Hashimoto's thyroiditis (HT), Graves' disease (GD), and thyroid cancer. Human sexual function and fertility are also affected by OS and TD. Hypothyroidism and hyperthyroidism diagnosed in pregnant women have a negative effect on pregnancy as it may increase the risk of miscarriage or fetus mortality. In the case of TD in the mother, fetal health is also at risk - neurodevelopment and cognitive function of the child may be impaired in its future life. This review presents thyroid function in the context of TD during pregnancy. The authors introduce OS and describe oxidative DNA lesions as a crucial marker of thyroid pathologies.