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Showing 1 to 20 of 24 for “"DNA lesion"”.
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Studies of DNA lesion-protein interactions : toward the development of DNA repair-inhibiting chemotherapeutic agents
Thesis (Ph. D.)--Massachusetts Institute of Technology, Division of Toxicology, 1996.
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Study of DNA damage on DNA G-quadruplexes and biophysical evaluation of the effects of modified bases (lesions) on their conformation and stability
<p>Exposure of DNA to reactive oxygen species (ROS) results in the modified nucleobases (lesions) as well as strand scissions under physiological conditions. Due to its lowest oxidation potential (1.29 eV), guanine is the most easily oxidisable nucleobase. Furthermore, it has been observed that the …
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Development of The Ark Assay For Quantitating Dna- Protein Crosslink Accumulation and Fanconi Anemia Pathway Involvement In The Repair Process
<p>DNA-protein crosslinks (DPCs) are a common DNA lesion naturally arising in cells, wherein protein becomes covalently and irreversibly bound to the DNA. Given their excessive size, these adducts present a significant challenge to replication and transcription, thus requiring timely and efficient …
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The functional and molecular characterisation of the novel DNA damage repair protein Bod1L
DNA damage induces MDC1 recruitment and establishes a signalling platform that mediates the DNA damage response (DDR). I show that Bod1L plays a central role in DDR by controlling MDC1 and PP2A-B56 localisation to damaged DNA. Bod1L depletion leads to micronuclei formation in undamaged cells and …
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REGULATORY MECHANISMS OF TRANSCRIPTION AND ASSOCIATED DNA REPAIR
… the degradation of RNA polymerase II stalled at DNA lesion facilitating the rapid repair of transcriptionally active genes through a process of transcription coupled repair (TCR). My studies have addressed the key question of the fate of RNA polymerase II stalled at a lesion. My findings show …
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Role of DNA Mismatch Repair in Disease-associated Trinucleotide Repeat Instability
… and neuromuscular diseases. The mechanism of DNA instability is believed to involve the formation of slipped-repeat structures, and ongoing expansion requires the presence of functional mismatch repair (MMR) proteins. It is known that MMR efficiency is affected by the structure of the DNA …
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Dissecting the Role of microRNAs in the Radiation Response of Human Prostate Cancer
… transition (EMT) and promoting DNA repair following radiation, we found that miR-875-5p reconstitution in PCa cells counteracted EMT and impaired DNA lesion clearance, mainly via impairment of EGFR-ZEB1 axis. Restoration of miR-205 was able to significantly enhance PCa …
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Using <i>Drosophila melanogaster</i> as a Whole-Model Animal System to Elucidate the Mechanism of Action of Novel Anticancer Agents
DNA-modifying agents compose a large portion of current and phased-out anticancer agents. Interaction with DNA is linked to high levels of side effects and poor selectivity between cancerous and normal cells. This lack of specificity leads to side effects. Our lab used a prodrug strategy to design …
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RESPONSE OF A NEIL1 DEFICIENT MURINE EPITHELIAL CELL LINE TO CHROMATE
DNA is constantly exposed to oxidants which can lead to nucleobase damage. Chromium is of particular interest as a DNA oxidant because of its abundance in the environment and the ease with which it can be taken into a cell. Chromate, Cr(VI), ions are taken up by a cell through relatively …
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RESPONSE OF A NEIL1 DEFICIENT MURINE EPITHELIAL CELL LINE TO CHROMATE
DNA is constantly exposed to oxidants which can lead to nucleobase damage. Chromium is of particular interest as a DNA oxidant because of its abundance in the environment and the ease with which it can be taken into a cell. Chromate, Cr(VI), ions are taken up by a cell through relatively …
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Consequences of Oxidative DNA Damage: Base-Pair Dissociation, Singlet Oxygenation and DNA-Protein Crosslinking
<p>8-Oxo-2′-deoxyguanosine (OG) is a common DNA lesion resulting from oxidatively generated damage and pairs with complementary cytidine (C) in Watson Crick base-pairing within duplex DNA. The WC-OG·C lesion, if not recognized or repaired, not only leads to G⋅C→T⋅A transversion mutations (through …
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Detection of Biologically Important Molecules
… detection of α-dicarbonyl compounds and a DNA lesion marker. These ongoing research projects will continue. New studies including optimizing sensing conditions and the elucidation of selective binding mechanism include future work.
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Identification and characterization of novel genes involved in DNA double strand break repair process in the yeast Saccharomyces cerevisiae
DNA Double Strand Break (DSB) is the most severe form of DNA lesion. Unrepaired DSBs and/or mutations in key DSB repair genes can lead to genomic instability, cancer or even cell death. DSBs can be repaired by two independent pathways; Homologous Recombination (HR) and Non-Homologous End Joining …
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Mechanisms of Oxidative Stress Resistance in Porphyromonas gingivalis W83
… comigratory protein <em>(bcp)</em> genes, DNA repair mechanisms and the unique hemin layer of <em>P. gingivalis. </em>We tested the physiological function of the isogenic <em>ahpC</em> and <em>bcp</em>mutants to hydrogen peroxide. When compared to the wild-type <em>P. gingivalis</em> W83, …
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Light-induced modulation of DNA recognition by the Rad4/XPC damage sensor protein.
… trigger the biological assembly/disassembly of DNA damage repair proteins on DNA. Specifically, this work focuses on photo-regulation of DNA damage recognition by the xeroderma pigmentosum C complex (XPC-Rad23B; Rad4-23 in yeast). Rad4/XPC specifically recognizes various bulky …
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Understanding cell fate decisions in response to 0⁶-Methylguanine DNA lesions
… challenged by both endogenous and exogenous DNA damaging agents. DNA damage, if left unrepaired, can give rise to permanent genetic alterations that ultimately increase our risk of cancer and other diseases. To combat these threats, eukaryotic cells activate a DNA damage response (DDR) that …
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Structural and Biochemical Investigation of Fanconi Anemia Pathway Activation
DNA interstrand-crosslinks (ICLs) are covalent links between complementary DNA strands that prevent their separation, interfering with fundamental cellular processes such as DNA replication and transcription. Consequently, these DNA lesions are highly toxic and the inability to repair them results …
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Quantifying the pro- and antimutagenic roles of DNA damage and repair
… by the fact that every alteration in the DNA results from failed or incorrect repair of a DNA lesion, hence there are two factors which jointly shape the mutational spectrum of any mutagenic process. In this thesis, I quantify the variability of mutational signatures in model organisms and …
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Excited state charge redistribution and dynamics of flavins, flavorproteins, and their cofactors
… dinucleotide (FAD) bound to the light activated DNA repair enzyme DNA photolyase have been studied previously by this technique. This work focuses on the catalytically active form, the two-electron reduced anion. To facilitate analysis of this experiment, the Stark spectra of a simple flavin …
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Role of DNA repair protein ERCC1 in skin cancer
… one of the major repair systems for removal of DNA lesions. The NER pathway has evolved mainly to repair UV-induced DNA damage and is also active against a broad range of endogenously generated oxidative lesions. Defects in NER result in the human inherited disorder xeroderma pigmentosum (XP), …
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