The 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.g., apurinic/apyrimidinic (AP) sites) and a bulkier 5′,8-cyclo-2′-deoxypurine (cdPu), which is not a substrate for BER, the repair efficiency of the first one may be affected. The cdPus’ influence on the efficiency of nuclear BER in xrs5 cells have been investigated using synthetic oligonucleotides with bi-stranded CDL (containing (5′S) 5′,8-cyclo-2′-deoxyadenosine (ScdA), (5′R) 5′,8-cyclo-2′-deoxyadenosine (RcdA), (5′S) 5′,8-cyclo-2′-deoxyguanosine (ScdG) or (5′R) 5′,8-cyclo-2′-deoxyguanosine (RcdG) in one strand and an AP site in the other strand at different interlesion distances). Here, for the first time, the impact of ScdG and RcdG was experimentally tested in the context of nuclear BER. This study shows that the presence of RcdA inhibits BER more than ScdA; however, ScdG decreases repair level more than RcdG. Moreover, AP sites located ≤10 base pairs to the cdPu on its 5′-end side were repaired less efficiently than AP sites located ≤10 base pairs on the 3′-end side of cdPu. The strand with an AP site placed opposite cdPu or one base in the 5′-end direction was not reconstituted for cdA nor cdG. CdPus affect the repair of the other lesion within the CDL. It may translate to a prolonged lifetime of unrepaired lesions leading to mutations and impaired cellular processes. Therefore, future research should focus on exploring this subject in more detail.
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.
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.
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).
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.
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