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The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
provided by the
Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 11 to 19 of 19 (0.074 seconds)| 11 |
A Study of Mutagenesis by Translesion Synthesis DNA Polymerases Using A Novel High-throughput Mutation Assay SystemChen, Yizhang January 2018 (has links)
No description available.
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Assessment And In Vitro Repair Of Damaged Dna Templates From Forensic StainsHall, Ashley 01 January 2005 (has links)
DNA extracted from biological stains is often intractable to analysis. This may due to a number of factors including a low copy number (LCN) of starting molecules, the presence of soluble inhibitors or damaged DNA templates. Remedies may be available to the forensic scientist to deal with LCN templates and soluble inhibitors but none presently exist for damaged DNA. In fact, only recently has the biochemical nature, the extent of DNA damage in physiological stains and the point at which the damage inflicted upon a particular sample precludes the ability to obtain a genetic profile for purposes of identification been examined. The primary aims of this work were first to ascertain the types of DNA damage encountered in forensically relevant stains, correlating the occurrence this damage with the partial or total loss of a genotype, and then to attempt the repair of the damage by means of in vitro DNA repair systems. The initial focus of the work was the detection of damage caused by exogenous, environmental sources, primarily UV irradiation, but also factors such as heat, humidity and microorganism growth. Results showed that the primary causes of the damage that resulted in profile loss were strand breaks, both single and double stranded, as well as modifications to the DNA structure that inhibited its amplification. Armed with this knowledge, the next focus was the repair of the damage by means of in vitro DNA systems. Efforts have been concentrated on single strand break/gap repair and translesion synthesis assays. By modifying the assays and employing various combinations of the systems, a genetic signature has been recovered from previously intractable samples. Additionally, the effects that various storage conditions have on the DNA in physiological stains stored in a laboratory were examined. The optimal long term storage conditions for biological evidence has been a matter of debate in the forensic community for some time. But, no comprehensive study had previously been undertaken to describe the effects of dehydration and temperature on degradation and the ability to obtain a genetic profile on bloodstains kept in different types of storage media at a range of temperatures. To examine this, bloodstains were either allowed to dry overnight or placed in the storage medium while still wet and were stored at room temperature, 4oC or 30oC for up to four years. Results showed that specimens dehydrated prior to storage were very stable, and these bloodstains showed no degradation or loss of a genetic profile for up to four years.
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Translesion Synthesis Mediated Replication Gap Suppression, A Cancer VulnerabilityNayak, Sumeet 22 July 2020 (has links)
Error-free DNA replication is paramount to maintaining genomic integrity. Despite being highly regulated, the process of DNA replication is often challenged by various intrinsic and extrinsic sources of replication stress. Failure to maintain the DNA replication quality reduces genomic stability, cell survival and results in diseases, such as cancer. Thus, cells rely on the replication stress response that detects perturbations in DNA replication and pauses or arrests cellular replication. Similar to other intrinsic replication obstacles, oncogene expression also induces the replication stress response that acts as a barrier to cancer, thereby mystifying how cancer develops.
Here, we demonstrate that oncogene expression, similar to other replication stress inducing agents, induces single-stranded DNA (ssDNA) gaps that reduce cell fitness unless counteracted by translesion synthesis (TLS). Moreover, we find that TLS subverts the replication stress response in a wide range of cancer cell lines indicating that TLS is a previously unappreciated and unique cancer vulnerability. Mechanistically, we reveal that upon replication stress, TLS restricts replication fork slowing, reversal, and fork degradation, while maintaining continuous replication. Furthermore, we demonstrate that a small molecule inhibitor targeting the TLS factor, REV1, not only disrupts DNA replication and cancer cell fitness, but also synergizes with other therapies that induce replication gaps. Thus, our study places TLS at the center of cancer cell fitness as a necessary adaptation to overcome replication stress.
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Multiple Genotoxic Agents Activate ATR Kinase Signaling in Quiescent Human CellsMadkhali, Mariyyah Ahmed O. 18 May 2020 (has links)
No description available.
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Single-molecule studies of bacterial DNA replication and translesion synthesisZhao, Gengjing January 2018 (has links)
Faithful replication of genomic DNA is crucial for the survival of a cell. In order to achieve high-level accuracy in copying its genome, all cells employ replicative DNA polymerases that have intrinsic high fidelity. When an error occurs on the template DNA strand, in the form of lesions caused by diverse chemicals, reactive oxygen species, or UV light, the high-fidelity replicative DNA polymerases are stalled. To bypass these replication blocks, cells harbor multiple specialized translesion DNA polymerases that are error-prone and therefore able to accommodate the lesions and continue DNA synthesis. As a result of their low fidelity, the translesion polymerases are associated with increased mutagenesis, drug resistance, and cancer. Therefore, the access of the translesion polymerases to DNA needs to be tightly controlled, but how this is achieved has been the subject of debate. This Thesis presents the development of a co-localization single-molecule spectroscopy (CoSMoS) method to directly visualize the loading of the Escherichia coli replicative polymerase on DNA, as well as the exchange between the replicative polymerase and the translesion polymerases Pol II and Pol IV. In contrast to the toolbelt model for the exchange between the polymerases, this work shows that the translesion polymerases Pol II and Pol IV do not form a stable complex with the replicative polymerase Pol IIIα on the β-clamp. Furthermore, we find that the sequential activities of the replication proteins: clamp loader, clamp, and Pol IIIα, are highly organized while the exchange with the translesion polymerases is disordered. This exchange is not determined by lesion-recognition but instead a concentration-dependent competition between the replicative and translesion polymerases for the hydrophobic groove on the surface of the β-clamp. Hence, our results provide a unique insight into the temporal organization of events in DNA replication and translesion synthesis.
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A Multi-Disciplinary Investigation of Essential DNA Replication ProteinsGadkari, Varun V. 03 August 2017 (has links)
No description available.
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Zur Funktion des MPH1-Gens von Saccharomyces cerevisiae bei der rekombinativen Umgehung von replikationsarretierenden DNA-Schäden / On the function of the MPH1 gene from Saccharomyces cerevisiae in recombinational bypass of replication arresting DNA lesionsSchürer, Anke 22 January 2004 (has links)
No description available.
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The kinase MK2 in DNA replication upon genotoxic stress and chemotherapy / Die Kinase MK2 in der DNA-Replikation nach genotoxischem Stress und ChemotherapieKöpper, Frederik 17 October 2012 (has links)
No description available.
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Untersuchungen zur Funktion der Gene MPH1 und MMS2 aus Saccharomyces cerevisiae bei der fehlerfreien Umgehung von replikationsarretierenden DNA-Schäden / Studies on functions of the genes MPH1 and MMS2 from Saccharomyces cerevisiae during error free bypass of replication blocking DNA-lesionsEde, Christopher 13 January 2010 (has links)
No description available.
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