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Showing 1 to 20 of 86 for “"DNA lesions"”.
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Biological Consequences Of Complex Dna Lesions Induced By Bis-Electrophiles
Genomic DNA is constantly modified by bis–electrophiles which induce a wide array of DNA adducts. DNA adducts can threaten cell viability and genomic integrity by interfering with DNA replication and transcription. Unless repaired, they can be misread by DNA polymerases, leading to heritable …
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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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Role of TLS Polymerases in Replication of DNA Lesions in Human Cells
… are constantly exposed to numerous genotoxic lesions that inhibit replication. The inability of cells to correctly repair these lesions results in mutations or chromosomal aberrations that threaten the integrity of the genome. DNA damage tolerance mechanisms, including translesion synthesis …
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Formation and repair of DNA lesions : studies of oxidized cytosines and aflatoxin B₁ adducts
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemistry, 1998.
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Residual restoration of DNA lesions in Deinococcus radiodurans mutants indicate presence of a bypass UV-repair process
… strain to repair up to 80% of the total induced DNA photoproducts. Nucleotide excision repair (NER) is given priority over homologeous recombination repair (HR), based on the fact that 1R1A (recA) resumed repair of bipyrimidine dimers but UVs78 (uvrA-1 uvsE) did not repair any photoproduct type. …
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ARTEMIS AND METNASE MEDIATED PROCESSING OF 3΄-BLOCKED DNA LESIONS: ROLE IN RADIO/CHEMORESISTANCE AND DNA REPAIR
<p>DNA double-strand breaks (DSB) with chemically modified end-termini are the most significant lesions resulting from radio/chemotherapeutic intervention of cancer and non homologous end-joining (NHEJ) factor Artemis nuclease has been implicated in the repair of such breaks. To examine whether the …
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Homology-Directed Repair of Dna Lesions Generated by the Mismatch Repair Dependent Processing of Cytotoxic Guanine Adducts
… in chemotherapy and kill cancer cells by causing DNA damage. The O6-methylating anticancer drugs procarbazine, dacarbazine, and temozolomide generate O6-MeG adducts, while a thiopurine antimetabolite 6-thioguanine (6-thioG) generates S6-MeG DNA adducts. Instead of pairing with cytosine, these …
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Translesion synthesis and mutations: On the mutagenic properties of the two DNA lesions, 8-oxo-G and Pt-GG, and the functions of Y-family DNA polymerases and Rev3L on the bypass of each of the DNA lesions in mammalian cells
I studied the capabilities of the two DNA lesions 8-oxo-guanine and cisplatin intrastrand crosslinked 1,2-d(GpG) or Pt-GG to cause mutations in mammalian cells. Using isogenic cell lines generated from mice with selective gene knockouts of distinct DNA polymerases as models, I deduced the …
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The dynamic interplay between DNA damage and metabolism : the metabolic fate and transport of DNA lesions and novel DNA damage derived from intermediary metabolism
… two novel and complementary facets of endogenous DNA damage: the development of biomarkers of inflammation based on metabolites of DNA damage products and the formation of DNA adducts by electrophilic products of intermediary metabolism. From the first perspective, endogenous DNA damage generated …
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Next-generation sequencing as a tool for investigating the in vivo biological consequences of DNA lesions and its applications on the ethenoguanine, 8-oxoguanine and 1,3-butadiene-induced lesions
DNA damaging agents produce a plethora of DNA lesions, which can lead to various outcomes. In order to understand the biological consequences of DNA lesions, and hence gain insights into the carcinogenic mechanisms of DNA damaging agents, individual lesions need to be evaluated for their genotoxic …
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Novel regulatory mechanisms of mutagenic translesion DNA synthesis : characterization of REV1 in Saccharomyces cerevisiae
Cells are constantly subjected to DNA damage from endogenous and exogenous sources. Spontaneous DNA damage alone accounts for -30,000 DNA lesions per day in a mammalian cell. Cells are also exposed to an enormous variety of environmental agents that can cause a wide range of modified bases and …
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Transcription Coupled DNA Repair in Saccharomyces Cerevisiae: the Interplay of Facilitators and Repressors
… that removes bulky and/or helix-distorting DNA lesions, such as UV induced cyclobutane pyrimidine dimers (CPDs) and bulky chemical adducts. Transcription coupled repair (TCR) is a subpathway of NER dedicated to rapid removal of lesions in the transcribed strand of actively transcribed genes. …
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Interrogating DNA replication stress and DNA damage responses via phenotypic and functional CRISPR/Cas9 screens
DNA double-strand breaks are believed to be one of the most cytotoxic DNA lesions, posing a constant threat for genome integrity and cell survival. Consequently, various DNA repair processes and pathways have evolved to deal with different DNA lesions and ensure genome stability. The tumour …
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Function of Znf668 In Cancer Development
… and degradation; ZNF668 deficiency impairs DNA damage-induced p53 stabilization. Notably, ZNF668 effectively suppresses breast cancer cell proliferation and transformation <em>in vitro </em>and tumorigenicity <em>in vivo</em>. Consistently, ZNF668 knockdown readily transforms normal mammary …
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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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Targeted Drug Discovery: Targeting a Specific Conformation of MutS/MSH Proteins with Small Molecules
Mismatch repair proteins repair mismatches in the DNA and signal cell death in response to certain DNA lesions. Due to these distinct functions of MMR proteins, they are proposed to exist in at least two different conformations, "repair" and "death." The goal of this study was to exploit the …
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Identification and Investigation of Novel DNA Damage Repair Genes Via Network Analysis
While most DNA lesions are repaired faithfully and without genotoxic effect, double-stranded breaks (DSBs) are exceptional. The deleterious potential of a misrepaired DSB represents a severe threat to cellular integrity. Repair machinery defects are frequently observed in tumorigenic and oncogenic …
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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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Identification of Artemis and PARP-1 interacting factors: A yeast two hybrid screening approach
… of the cell is under the constant threat of DNA damage from endogenous and exogenous sources. In response to DNA damage mammalian cells elicit a highly complex, yet coordinated series of cellular responses, which are triggered by the detection of DNA lesions and ultimately lead to cell …
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