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 × 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 dGoxodG 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 ATCG 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.






Karwowski BT




Has Abstract


2020-02-12 00:00:00












  • GSK3β: A Master Player in Depressive Disorder Pathogenesis and Treatment Responsiveness.

    abstract::Glycogen synthase kinase 3β (GSK3β), originally described as a negative regulator of glycogen synthesis, is a molecular hub linking numerous signaling pathways in a cell. Specific GSK3β inhibitors have anti-depressant effects and reduce depressive-like behavior in animal models of depression. Therefore, GSK3β is sugge...


    pub_type: 杂志文章,评审


    authors: Duda P,Hajka D,Wójcicka O,Rakus D,Gizak A

    更新日期:2020-03-16 00:00:00

  • Interleukin 26 Skews Macrophage Polarization Towards M1 Phenotype by Activating cJUN and the NF-κB Pathway.

    abstract::Interleukin 26 (IL-26) is a new member of the IL-10 family that is highly expressed in rheumatoid arthritis (RA). However, the functions of IL-26 produced by macrophages in RA have not been elucidated. In the present work, we evaluated the effects and the mechanisms of IL-26 on M1 and M2 macrophage differentiation. Hu...


    pub_type: 杂志文章


    authors: Lin YH,Wang YH,Peng YJ,Liu FC,Lin GJ,Huang SH,Sytwu HK,Cheng CP

    更新日期:2020-04-10 00:00:00

  • Epigenomic Dysregulation in Schizophrenia: In Search of Disease Etiology and Biomarkers.

    abstract::Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have ...


    pub_type: 杂志文章,评审


    authors: Khavari B,Cairns MJ

    更新日期:2020-08-05 00:00:00

  • Mitochondrial Metabolism in Major Neurological Diseases.

    abstract::Mitochondria are bilayer sub-cellular organelles that are an integral part of normal cellular physiology. They are responsible for producing the majority of a cell's ATP, thus supplying energy for a variety of key cellular processes, especially in the brain. Although energy production is a key aspect of mitochondrial ...


    pub_type: 杂志文章,评审


    authors: Zhou Z,Austin GL,Young LEA,Johnson LA,Sun R

    更新日期:2018-11-23 00:00:00

  • GABAB Receptors Augment TRPC3-Mediated Slow Excitatory Postsynaptic Current to Regulate Cerebellar Purkinje Neuron Response to Type-1 Metabotropic Glutamate Receptor Activation.

    abstract::During strong parallel fiber stimulation, glutamate released at parallel fiber-Purkinje cell synapses activates type-1 metabotropic glutamate receptor (mGluR1) to trigger a slow excitatory postsynaptic current (sEPSC) in cerebellar Purkinje neurons. The sEPSC is mediated by transient receptor potential canonical 3 (TR...


    pub_type: 杂志文章


    authors: Tian J,Zhu MX

    更新日期:2018-07-29 00:00:00

  • Activation of Human γδ T Cells: Modulation by Toll-Like Receptor 8 Ligands and Role of Monocytes.

    abstract:BACKGROUND:Human Vγ9Vδ2 γδ T cells can kill a variety of cancer cells and have attracted substantial interest for cancer immunotherapy. Toll-like receptor (TLR) ligands are promising adjuvants for cancer immunotherapy, but TLR7/8 ligand Resiquimod has been shown to inhibit CD4 T-cell activation in a monocyte-dependent ...


    pub_type: 杂志文章


    authors: Serrano R,Wesch D,Kabelitz D

    更新日期:2020-03-13 00:00:00

  • Zebrafish Avatars towards Personalized Medicine-A Comparative Review between Avatar Models.

    abstract::Cancer frequency and prevalence have been increasing in the past decades, with devastating impacts on patients and their families. Despite the great advances in targeted approaches, there is still a lack of methods to predict individual patient responses, and therefore treatments are tailored according to average resp...


    pub_type: 杂志文章,评审


    authors: Costa B,Estrada MF,Mendes RV,Fior R

    更新日期:2020-01-25 00:00:00

  • Automated Counting of Cancer Cells by Ensembling Deep Features.

    abstract::High-content and high-throughput digital microscopes have generated large image sets in biological experiments and clinical practice. Automatic image analysis techniques, such as cell counting, are in high demand. Here, cell counting was treated as a regression problem using image features (phenotypes) extracted by de...


    pub_type: 杂志文章


    authors: Liu Q,Junker A,Murakami K,Hu P

    更新日期:2019-09-02 00:00:00

  • p53 -Dependent and -Independent Nucleolar Stress Responses.

    abstract::The nucleolus has emerged as a cellular stress sensor and key regulator of p53-dependent and -independent stress responses. A variety of abnormal metabolic conditions, cytotoxic compounds, and physical insults induce alterations in nucleolar structure and function, a situation known as nucleolar or ribosomal stress. R...


    pub_type: 杂志文章


    authors: Holmberg Olausson K,Nistér M,Lindström MS

    更新日期:2012-10-15 00:00:00

  • Rho GTPases in the Amygdala-A Switch for Fears?

    abstract::Fear is a fundamental evolutionary process for survival. However, excess or irrational fear hampers normal activity and leads to phobia. The amygdala is the primary brain region associated with fear learning and conditioning. There, Rho GTPases are molecular switches that act as signaling molecules for further downstr...


    pub_type: 杂志文章,评审


    authors: Sarowar T,Grabrucker AM

    更新日期:2020-08-26 00:00:00

  • 3D Telomere Structure Analysis to DetectGenomic Instability and Cytogenetic Evolutionin Myelodysplastic Syndromes.

    abstract::The disease course of myelodysplastic syndromes (MDS) features chromosome instability and clonal evolution, leading to the sequential acquisition of novel cytogenetic aberrations and the accumulation of these abnormalities in the bone marrow. Although clonal cytogenetic abnormalities can be detected by conventional cy...


    pub_type: 杂志文章


    authors: Rangel-Pozzo A,Corrêa de Souza D,Schmid-Braz AT,de Azambuja AP,Ferraz-Aguiar T,Borgonovo T,Mai S

    更新日期:2019-04-02 00:00:00

  • Hypothermia Advocates Functional Mitochondria and Alleviates Oxidative Stress to Combat Acetaminophen-Induced Hepatotoxicity.

    abstract::For years, moderate hypothermia (32 °C) has been proposed as an unorthodox therapy for liver injuries, with proven hepatoprotective potential. Yet, limited mechanistic understanding has largely denied its acceptance over conventional pharmaceuticals for hepatoprotection. Today, facing a high prevalence of acetaminophe...


    pub_type: 杂志文章


    authors: Tan YL,Ho HK

    更新日期:2020-10-26 00:00:00

  • An Intricate Connection between Alternative Splicing and Phenotypic Plasticity in Development and Cancer.

    abstract::During tumor progression, hypoxia, nutrient deprivation or changes in the extracellular environment (i.e., induced by anti-cancer drugs) elicit adaptive responses in cancer cells. Cellular plasticity increases the chance that tumor cells may survive in a challenging microenvironment, acquire new mechanisms of resistan...


    pub_type: 杂志文章,评审


    authors: Biamonti G,Infantino L,Gaglio D,Amato A

    更新日期:2019-12-21 00:00:00

  • Transcriptional Suppression of the NLRP3 Inflammasome and Cytokine Release in Primary Macrophages by Low-Dose Anthracyclines.

    abstract::Tissue-resident macrophages play critical roles in controlling homeostasis, tissue repair, and immunity. Inflammatory macrophages can sustain tissue damage and promote the development of fibrosis during infections and sterile tissue injury. The NLRP3 inflammasome and its effector cytokine IL-1β have been identified as...


    pub_type: 杂志文章


    authors: Köse-Vogel N,Stengel S,Gardey E,Kirchberger-Tolstik T,Reuken PA,Stallmach A,Bruns T

    更新日期:2019-12-28 00:00:00

  • HDAC6 Regulates Radiosensitivity of Non-Small Cell Lung Cancer by Promoting Degradation of Chk1.

    abstract::We have previously discovered that HDAC6 regulates the DNA damage response (DDR) via modulating the homeostasis of a DNA mismatch repair protein, MSH2, through HDAC6's ubiquitin E3 ligase activity. Here, we have reported HDAC6's second potential E3 ligase substrate, a critical cell cycle checkpoint protein, Chk1. We h...


    pub_type: 杂志文章


    authors: Moses N,Zhang M,Wu JY,Hu C,Xiang S,Geng X,Chen Y,Bai W,Zhang YW,Bepler G,Zhang XM

    更新日期:2020-10-04 00:00:00

  • Role of Notch Receptors in Hematologic Malignancies.

    abstract::Notch receptors are single-pass transmembrane proteins that play a critical role in cell fate decisions and have been implicated in the regulation of many developmental processes. The human Notch family comprises of four receptors (Notch 1 to 4) and five ligands. Their signaling can regulate extremely basic cellular p...


    pub_type: 杂志文章,评审


    authors: Gragnani L,Lorini S,Marri S,Zignego AL

    更新日期:2020-12-24 00:00:00

  • Angiogenic Effects of Human Dental Pulp and Bone Marrow-Derived Mesenchymal Stromal Cells and their Extracellular Vesicles.

    abstract::Blood vessel formation or angiogenesis is a key process for successful tooth regeneration. Bone marrow-derived mesenchymal stromal cells (BM-MSCs) possess paracrine proangiogenic properties, which are, at least partially, induced by their extracellular vesicles (EVs). However, the isolation of BM-MSCs is associated wi...


    pub_type: 杂志文章


    authors: Merckx G,Hosseinkhani B,Kuypers S,Deville S,Irobi J,Nelissen I,Michiels L,Lambrichts I,Bronckaers A

    更新日期:2020-01-28 00:00:00

  • microRNAs and Cardiac Cell Fate.

    abstract::The role of small, non-coding microRNAs (miRNAs) has recently emerged as fundamental in the regulation of the physiology of the cardiovascular system. Several specific miRNAs were found to be expressed in embryonic, postnatal, and adult cardiac tissues. In the present review, we will provide an overview about their ro...


    pub_type: 杂志文章,评审


    authors: Piubelli C,Meraviglia V,Pompilio G,D'Alessandra Y,Colombo GI,Rossini A

    更新日期:2014-08-05 00:00:00

  • BAG3 Proteomic Signature under Proteostasis Stress.

    abstract::The multifunctional HSP70 co-chaperone BAG3 (BCL-2-associated athanogene 3) represents a key player in the quality control of the cellular proteostasis network. In response to stress, BAG3 specifically targets aggregation-prone proteins to the perinuclear aggresome and promotes their degradation via BAG3-mediated sele...


    pub_type: 杂志文章


    authors: Hiebel C,Stürner E,Hoffmeister M,Tascher G,Schwarz M,Nagel H,Behrends C,Münch C,Behl C

    更新日期:2020-11-04 00:00:00

  • Nitrogen Deficiency-Induced Decrease in Cytokinins Content Promotes Rice Seminal Root Growth by Promoting Root Meristem Cell Proliferation and Cell Elongation.

    abstract::Rice (Oryza sativa L.) seedlings grown under nitrogen (N) deficiency conditions show a foraging response characterized by increased root length. However, the mechanism underlying this developmental plasticity is still poorly understood. In this study, the mechanism by which N deficiency influences rice seminal root gr...


    pub_type: 杂志文章


    authors: Wang Q,Zhu Y,Zou X,Li F,Zhang J,Kang Z,Li X,Yin C,Lin Y

    更新日期:2020-04-09 00:00:00

  • Nuclear Isoforms of Neurofibromin Are Required for Proper Spindle Organization and Chromosome Segregation.

    abstract::Mitotic spindles are highly organized, microtubule (MT)-based, transient structures that serve the fundamental function of unerring chromosome segregation during cell division and thus of genomic stability during tissue morphogenesis and homeostasis. Hence, a multitude of MT-associated proteins (MAPs) regulates the dy...


    pub_type: 杂志文章


    authors: Peta C,Tsirimonaki E,Samouil D,Georgiadou K,Mangoura D

    更新日期:2020-10-23 00:00:00

  • HIF-1α and HIF-2α Differently Regulate the Radiation Sensitivity of NSCLC Cells.

    abstract::The hypoxia-inducible transcription factors (HIF)-1/2α are the main oxygen sensors which regulate the adaptation to intratumoral hypoxia. The aim of this study was to assess the role of the HIF proteins in regulating the radiation response of a non-small cell lung cancer (NSCLC) in vitro model. To directly assess the ...


    pub_type: 杂志文章


    authors: Moreno Roig E,Groot AJ,Yaromina A,Hendrickx TC,Barbeau LMO,Giuranno L,Dams G,Ient J,Olivo Pimentel V,van Gisbergen MW,Dubois LJ,Vooijs MA

    更新日期:2019-01-12 00:00:00

  • Fibronectin Regulation of Integrin B1 and SLUG in Circulating Tumor Cells.

    abstract::Metastasis is the leading cause of cancer death worldwide. Circulating tumor cells (CTCs) are a critical step in the metastatic cascade and a good tool to study this process. We isolated CTCs from a syngeneic mouse model of hepatocellular carcinoma (HCC) and a human xenograft mouse model of castration-resistant prosta...


    pub_type: 杂志文章


    authors: Huaman J,Naidoo M,Zang X,Ogunwobi OO

    更新日期:2019-06-20 00:00:00

  • Newborn Screening Samples for Diabetes Research: An Underused Resource.

    abstract::Inborn errors of metabolism and diabetes share common derangements in analytes of metabolic networks that are tested for in newborn screening, usually performed 48-72 h after birth. There is limited research examining the metabolic imprint of diabetes on newborn screening results. This paper aims to demonstrate the li...


    pub_type: 杂志文章,评审


    authors: Estrella JFGL,Immanuel J,Wiley V,Simmons D

    更新日期:2020-10-15 00:00:00

  • Dissecting Aging and Senescence-Current Concepts and Open Lessons.

    abstract::In contrast to the programmed nature of development, it is still a matter of debate whether aging is an adaptive and regulated process, or merely a consequence arising from a stochastic accumulation of harmful events that culminate in a global state of reduced fitness, risk for disease acquisition, and death. Similarl...


    pub_type: 杂志文章,评审


    authors: Schmeer C,Kretz A,Wengerodt D,Stojiljkovic M,Witte OW

    更新日期:2019-11-15 00:00:00

  • Activation of Cryptic 3' Splice-Sites by SRSF2 Contributes to Cassette Exon Skipping.

    abstract::Here we show that the serine/arginine rich splicing factor 2 (SRSF2) promotes cryptic 3' splice-site (3'AG') usage during cassette exon exclusion in survival of motor neuron (SMN2) minigenes. Deletion of the 3'AG' (3'AG'1), its associated branch point (BP') and polypyrimidine tract (PPT') sequences directs SRSF2 to pr...


    pub_type: 杂志文章


    authors: Moon H,Jang HN,Liu Y,Choi N,Oh J,Ha J,Zheng X,Shen H

    更新日期:2019-07-10 00:00:00

  • GhVTC1, the Key Gene for Ascorbate Biosynthesis in Gossypium hirsutum, Involves in Cell Elongation Under Control of Ethylene.

    abstract::L-Ascorbate (Asc) plays important roles in cell growth and plant development, and its de novo biosynthesis was catalyzed by the first rate-limiting enzyme VTC1. However, the function and regulatory mechanism of VTC1 involved in cell development is obscure in Gossypium hirsutum. Herein, the Asc content and AsA/DHA rati...


    pub_type: 杂志文章


    authors: Song W,Wang F,Chen L,Ma R,Zuo X,Cao A,Xie S,Chen X,Jin X,Li H

    更新日期:2019-09-05 00:00:00

  • The BMP Receptor 2 in Pulmonary Arterial Hypertension: When and Where the Animal Model Matches the Patient.

    abstract::Background: Mutations in bone morphogenetic protein receptor type II (BMPR2) are leading to the development of hereditary pulmonary arterial hypertension (PAH). In non-hereditary forms of PAH, perturbations in the transforming growth factor-β (TGF-β)/BMP-axis are believed to cause deficient BMPR2 signaling by changes ...


    pub_type: 杂志文章


    authors: Happé C,Kurakula K,Sun XQ,da Silva Goncalves Bos D,Rol N,Guignabert C,Tu L,Schalij I,Wiesmeijer KC,Tura-Ceide O,Vonk Noordegraaf A,de Man FS,Bogaard HJ,Goumans MJ

    更新日期:2020-06-08 00:00:00

  • Animal, Fungi, and Plant Genome Sequences Harbor Different Non-Canonical Splice Sites.

    abstract::Most protein-encoding genes in eukaryotes contain introns, which are interwoven with exons. Introns need to be removed from initial transcripts in order to generate the final messenger RNA (mRNA), which can be translated into an amino acid sequence. Precise excision of introns by the spliceosome requires conserved din...


    pub_type: 杂志文章


    authors: Frey K,Pucker B

    更新日期:2020-02-18 00:00:00

  • Carbonic Anhydrase III Promotes Cell Migration and Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma.

    abstract::Epithelial-mesenchymal transition (EMT) is strongly correlated with tumor metastasis and contains several protein markers, such as E-cadherin. Carbonic anhydrase III (CA III) exhibits low carbon dioxide hydratase activity in cancer. However, the detailed mechanisms of CA III and their roles in oral cancer are still un...


    pub_type: 杂志文章


    authors: Chu YH,Su CW,Hsieh YS,Chen PN,Lin CW,Yang SF

    更新日期:2020-03-13 00:00:00