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 (dG), with an oxidation potential that is 0.
View Article and Find Full Text PDFManuka 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.
View Article and Find Full Text PDFThe 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 (dG) on the charge transfer through the double helix as well as their electronic properties were investigated.
View Article and Find Full Text PDFThe 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 (Ia) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (dG) on the spatial geometry, electronic properties, and ds-DNA charge transfer. The ground stage of a d[AIaAGA]*d[TCTCT] 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.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFVitamin B12 plays a key role in DNA stability. Research indicates that vitamin B12 deficiency leads to indirect DNA damage, and vitamin B12 supplementation may reverse this effect. Vitamin B12 acts as a cofactor for enzymes such as methionine synthase and methylmalonyl-CoA mutase, which are involved in DNA methylation and nucleotide synthesis.
View Article and Find Full Text PDFGenetic information stored in a DNA base sequence is continuously exposed to harmful factors. It has been determined that 9 × 10 different DNA damage events occur in a single human cell every 24 h. Of these, 7,8-dihydro-8-oxo-guanosine (G) is one of the most abundant and can undergo further transformations towards spirodi(iminohydantoin) (Sp).
View Article and Find Full Text PDFThe genetic information stored in the nucleobase sequence is continuously exposed to harmful extra- and intra-cellular factors, which can lead to different types of DNA damage, with more than 70 lesion types identified so far. In this article, the influence of a multi-damage site containing (5'/) 5',8-cyclo-2'-deoxyguanosine (cdG) and 7,8-dihydro-8-oxo-2'-deoxyguanosine (dG) on charge transfer through ds-DNA was taken into consideration. The spatial geometries of oligo-RcdG: d[A(5')cGAGA]*d[TCTCT] and oligo-ScdG: d[A(5')cGAGA]*d[TCTCT] were optimized at the M06-2X/6-D95**//M06-2X/sto-3G level of theory in the aqueous phase using ONIOM methodology.
View Article and Find Full Text PDFAccumulation 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.
View Article and Find Full Text PDFGenetic 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, G and G have been identified as the most abundant in normoxic and hypoxic conditions, respectively. This article considers d[AGAGA]*[TCTCT] (oligo-G) 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.
View Article and Find Full Text PDFEvery 24 h, roughly 3 × 10 incidences of DNA damage are generated in the human body as a result of intra- or extra-cellular factors. The structure of the formed lesions is identical to that formed during radio- or chemotherapy. Increases in the clustered DNA damage (CDL) level during anticancer treatment have been observed compared to those found in untreated normal tissues.
View Article and Find Full Text PDFGenetic 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.
View Article and Find Full Text PDFVitamin K is the common name for a group of compounds recognized as essential for blood clotting. The group comprises phylloquinone (K1)-a 2-methyl-3-phytyl-1,4-naphthoquinone; menaquinone (K2, MK)-a group of compounds with an unsaturated side chain in position 3 of a different number of isoprene units and a 1,4-naphthoquinone group and menadione (K3, MD)-a group of synthetic, water-soluble compounds 2-methyl-1,4-naphthoquinone. However, recent epidemiological studies suggest that vitamin K has various benefits that go beyond blood coagulation processes.
View Article and Find Full Text PDFIonizing radiation induces DNA damage, including characteristic clusters and tandem lesions e.g., 5',8-cyclo-2'-deoxyPurines (cdPus).
View Article and Find Full Text PDFHuman genome is exposed to the variety of damaging factors, such as ionizing radiation. 5',8-cyclo-2'-deoxypurines (cdPus) are well described unfavorable outcomes of DNA damage, especially devastating as a part of clustered DNA lesions (CDL). Since cdPus are not repaired by base excision repair (BER) and poorly repaired by nucleotide excision repair (NER), it is important to unveil the mechanisms of cdPus action within the genome.
View Article and Find Full Text PDFThe 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.
View Article and Find Full Text PDFClustered DNA lesions (CDL) containing 5',8-cyclo-2'-deoxypurines (cdPus) are an example of extensive abnormalities occurring in the DNA helix and may impede cellular repair processes. The changes in the efficiency of nuclear base excision repair (BER) were investigated using (a) two cell lines, one of the normal skin fibroblasts as a reference (BJ) and the second from patients' skin (XPC), and (b) synthetic oligonucleotides with single- and double-stranded CDL (containing 5',8-cyclo-2'-deoxyadenosine (cdA) and the abasic (AP) site at various distances between lesions). The nuclear BER has been observed and the effect of both cdA isomers (5' and 5') presence in the DNA was tested.
View Article and Find Full Text PDFIonizing 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).
View Article and Find Full Text PDFRestriction 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.
View Article and Find Full Text PDFAs a result of external and endocellular physical-chemical factors, every day approximately ~10 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.
View Article and Find Full Text PDFThe seed of life is concealed in the base sequence in DNA. This macromolecule is continuously exposed to harmful factors which can cause it damage. The stability of genetic information depends on the protein efficiency of repair systems.
View Article and Find Full Text PDFThe clustered DNA lesions (CDLs) are a characteristic feature of ionizing radiation's impact on the human genetic material. CDLs impair the efficiency of cellular repair machinery, especially base excision repair (BER). When CDLs contain a lesion repaired by BER (e.
View Article and Find Full Text PDFMicronutrients such as vitamins and trace elements are crucial for maintaining the health of all organisms. Micronutrients are involved in every cellular/biochemical process. They play roles in proper heart and brain functioning, influence immunological responses, and antioxidant defense systems.
View Article and Find Full Text PDFOne 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.
View Article and Find Full Text PDFThe 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.
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