Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 19 of 19 for “"interstrand crosslinks"”.
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Defining the role of endonuclease VIII-like 1 and 3 in the repair of interstrand crosslinks in cancer cells
… (FANC) proteins involved in the repair of DNA interstrand crosslinks (ICLs). More recently, two DNA glycosylases (endonuclease VIII – like 1 & 3 [NEIL1 & NEIL3]) that excise oxidised bases from DNA, thus initiating base excision repair, have been found to participate in the resolution of …
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Understanding of Intrinsic Sources of DNA Damage that Drive Human Disease: A Foray into the Study of DNA Interstrand Crosslinks and Genome-Embedded Ribonucleotides
… focus on two types of endogenous DNA damage: 1) interstrand crosslinks (ICLs) formed by DNA damaging aldehydes and 2) genome-embedded ribonucleotides. The clinical pathologies arising in the setting of the improper removal or repair of ICLs or genome-embedded ribonucleotides are diverse. A …
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A study of the formation of interstrand and intrastrand crosslinks through abasic site and cleaved abasic site chemistry
… If left unrepaired, subsequent damages such as interstrand crosslinks or strand cleavage can arise. While numerous studies have been conducted on crosslinks and strand cleavage, there is still much unknown information that warrants further investigation. This dissertation will use the tools of …
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Elucidation of Snm1B Function
… Snm1B protects DNA from agents that induce interstrand crosslinks (ICLs), lethal lesions that covalently attach the opposite strands of DNA together. To elucidate how Snm1B performs these functions I performed a yeast two-hybrid screen to identify proteins binding to the C-terminus of Snm1B. …
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Modulated Functions of The Fanconi Anemia Core Complex
… are characterized by hypersensitivity to DNA interstrand crosslinks (ICLs), suggesting that FA genes play a role in ICL repair. Fanconi anemia core complex (including A, B, C, E, F, G, L, FAAP20, and FAAP100) activates the Fanconi pathway by providing the essential E3 ligase activity for …
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Investigating the role of protein ubiquitylation in the maintenance of genome stability
… step in the repair of other DNA lesions, such as interstrand crosslinks (ICLs). The importance of HR for maintaining genome stability is underscored by the observation that loss-of-function mutations in HR factors are commonly seen in human cancers. In this thesis, I report the use of a key …
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Clinical resistance to platinum chemotherapy in ovarian cancer
… remain to be established. We have studied DNA interstrand crosslinking and its repair in response to ex vivo treatment with cisplatin in forty patients with ovarian cancer using the single cell gel electrophoresis (comet) assay. Tumour cells from resected tumours or tumour and mesothelial cells …
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Nucleotide Excision Repair, Crosslink Repair and Transcriptional Function of Xpa In Human Cells
… enhances sensitivity of mammalian cells to DNA interstrand crosslinks (ICL)-generating agents. I found that XPA is retained on damaged DNA following exposure to UVA-activated psoralen, and investigated repair of a triplex forming oligonucleotide (TFO)-directed psoralen ICL. A TFO-directed …
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Analysis and confirmation of the results of a yeast two-hybrid screen carried out to identify proteins that interact with drosophila XRCC2
… of damage are double-strand breaks (DSBs) and interstrand crosslinks. A single DSB or crosslink can potentially kill a cell if it is not repaired~ In human and other vertebrate cells, DSBs are repaired by two different mechanisms. The nonhomologous end-joining pathway can bring together the …
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Regulation of Rad51D In Homologous Recombination Dna Repair by Alternative Splicing and Ubiquitin Modification
… repair of DNA double-stranded breaks and interstrand crosslinks. Understanding the processes that regulate HR will provide new insights into carcinogenesis and potentially identify new targets for therapeutic intervention. The work presented in this dissertation investigated two novel …
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Regulation of structure-selective nucleases by the SLX4 scaffold in ICL repair and HJ resolution
… shown to have essential roles in repair of DNA interstrand crosslinks (ICLs). In addition to its role in ICL repair, the SLX4 complex has the relatively unusual property of being able to cleave efficiently four-way DNA structures called Holliday junctions (HJs) in vitro. At the outset of this …
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Investigating the role of NEIL3 in colorectal cancer resistance to oxaliplatin
… where it produces DNA intra- and inter-strand crosslinks that prevent transcription and DNA replication to cause cell death. Although numerous mechanisms of tumour resistance to oxaliplatin have been reported, normal healthy cells also rely on the majority of these mechanisms for survival and …
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Low-grade aldehyde stress protects mice from diet-induced obesity
… metabolites that have been shown to cause interstrand crosslinks and transcriptional stress. In this work, the response to aldehyde stress of different strengths and in various contexts is analysed, which reveals the specificity of the DNA damage response *in vivo*. Aldehydes are produced …
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Investigating the Role of Reactive Aldehydes in the Development of Head and Neck Squamous Cell Carcinoma in Fanconi Anemia
… which is responsible for the repair of DNA interstrand crosslinks, is ubiquitously found in all tissues; however, FA patients lose the FA DNA repair pathway in all their tissues. Despite the absence of this pathway in all their tissues, the epithelium of the head and neck is …
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Molecular Characterization of Novel Mutations in Fanconi Anemia Patients
… are required for the proper repair of DNA interstrand crosslinks (ICL), a deleterious type of DNA damage that covalently binds DNA strands. We have used Whole Exome Sequencing (WES) in conjunction with cell-based assays to determine disease-causing mutations in a subset of patients enrolled …
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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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Investigation into ubiquitin signalling in response to cisplatin
… drug that acts by introducing toxic DNA interstrand crosslinks into proliferating cells, causing both cytostatic and cytotoxic effects. Although various models of the interstrand crosslink (ICL) response have been proposed, none of them are complete and much still remains unknown about …
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New Insights into the Roles of FAN1 Nuclease in Genome Maintenance and Disease
… two major threats to genomic stability: DNA interstrand crosslinks (ICLs), and the expansion of trinucleotide repeats. ICLs are highly deleterious lesions that disrupt replication, are destructive to dividing cells, and are extremely toxic to the hematopoietic system. The …
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Caretaker-Gen-Syndrome
… sich durch Hypersensitivität gegenüber DNA-„interstrand crosslinks“ (ICLs) aus, zu deren Behebung u.a. die homologe Rekombinationsreparatur (HRR) eingesetzt wird, bei der das RAD51(A)-Protein eine zentrale Rolle spielt. Aufgrund schwacher Homologien werden 5 weitere Proteine (RAD51B, C, D, …