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 20 of 58 for “"genome instability"”.
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The Role of 5-Hydroxymethylcytosine in Genome Instability
… mechanisms exist to remove 5mC from the genome. This is critical during developmental periods of widespread epigenetic reprogramming in the early zygote and primordial germ cells. DNA demethylation mechanisms may be passive, relying on dilution of 5mC with successive rounds of DNA …
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G/C tracts and genome instability in Caenorhabditis elegans
The integrity of the genome is critical to organisms and it is affected by many factors. Radiation, for example, poses a serious threat to genome stability of human beings. While physical monitors for radiation hazard are present, the biological consequences of long term exposure to radiation are …
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Genome Instability Associated with DNA Topoisomerase Activity during Gene Transcription
Las lesiones que se producen en el ADN suponen un desafío continuo para la integridad genómica, siendo las roturas de doble cadena del ADN (DSBs) la lesión más citotóxica para la célula. Numerosos estudios han mostrado recientemente que una fuente fisiológica de DSBs es la actividad de las …
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Biomarkers of Genome Instability and Disease Progression in Ovarian Cancer
… variants driven by extreme chromosomal instability (CIN). Importantly, CIN is a key mediator of clonal diversity which fuels the development of treatment resistance. An increased understanding of underlying mechanisms and mutational processes causing CIN in HGSOC is therefore critical to …
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The Origin of Genome Instability in Cancer: Role of the Fragile Site Gene Product FHIT
… Most cancers exhibit remarkable genomic instability, defined as an elevated rate of genetic mutation at the single nucleotide and chromosome levels. Genomic instability is a facilitating hallmark of cancer in that it raises the probability of generating cancer-promoting mutations. …
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The Fanconi anemia pathway and HELQ work alongside dormant replication origins to suppress replication-associated genome instability
… unchecked, this threatens the integrity of the genome and may be a driver of cancer development. Utilizing the <italic>Mcm4<super>chaos3</super></italic> mouse model, we found that dormant replication origins, which act as backup initiation sites, play a critical role in the recovery of stalled …
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RNA EXPORT FACTOR ELF1 MAINTAINS GENOME STABILITY IN FISSION YEAST
Genome instability, or frequent mutations within a genome, is deleterious and a hallmark of carcinogenesis. Here, I identified that Elf1, a AAA+ family ATPase involved in mRNA nuclear export, prevents genome instability. Upon deletion, elf1Δ cells grow slowly, forming small colonies. Curiously, …
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Mechanisms of cytosolic DNA sensing and neuroinflammation in ataxia-telangiectasia
Monogenic genome instability disorders are caused by loss-of-function mutations in genes critical for the DNA damage response. These disorders commonly present with neurological disease, exemplifying the importance of preserving genome stability in the central nervous system (CNS). …
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Genomic Instability and the Oncohistone H3K27M Drive Gliomagenesis in a Murine Model
<p>Maintaining genome stability is crucial for human health and it is of particular importance in neural cells during early brain development. Genome maintenance occurs at two broad stages; surveillance during DNA replication and DNA damage repair in differentiating and mature cells. Neural cells …
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A MOLECULAR UNDERSTANDING OF ANEUPLOID CELL CLEARANCE
… chromosome number associated with cancer and genome instability. My Ph.D. research focused on understanding the interplay between aneuploid cells and the immune system. By utilising mass spectrometry and the Surfaceome database, I identified plasma membrane molecules differentially expressed …
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A study of the formation of interstrand and intrastrand crosslinks through abasic site and cleaved abasic site chemistry
… When damaged, negative consequences such as genome instability or cell death can occur. One common, unavoidable, and highly reactive form of DNA damage is the formation of apurinic/apyrimidinic sites (known as abasic sites); which occur at least 10,000 times per cell per day. If left …
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TO INVESTIGATE THE ROLE OF RNF8 IN REGULATING MITOTIC PROGRESSION IN GLIOMAS
… blocks GSC mitotic progression and augments genome instability. Indeed, low RNF8 expression portends poor patient prognosis in glioma patients. Importantly, our mechanistic findings led to the rational combination of PLK1 and HSP90 inhibitors that elicit an additive effect in reducing GSC …
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Keep the ORCs at bay : how eukaryotic cells ensure one round of DNA replication per cell cycle
… eukaryotic cells must faithfully replicate their genome, ensuring exactly one full copy is made. Both under-replicating or over-replicating the genome can have deleterious consequences including cell death, genome instability and cancer. Thus, this process is tightly regulated. The major mechanism …
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Exploring the effects and efficacy of novel cell cycle regulating compounds in aggressive Breast, Ovarian and Cervical Cancer
… during mitosis. Defects in SAC can result in genome instability, increasing the risk of cancer development and making it a potential therapeutic target for cancer treatment. The commercial compounds Reversine (an Aurora kinase B and Mps1 inhibitor) and Apcin (an APC/C inhibitor) have been …
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The Crosstalk Between DNA Mismatch Repair and Replication
… replication stress response to promote genome instability when replication forks are filled with biosynthetic errors. The importance of MMR in maintaining genome stability prompts us to further study the mechanism of MMR in vitro, particularly how the MMR initiation complex is formed in …
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Identification of MMS22 as a regulator of DNA repair
… DNA replication forks. This is a major source of genome instability that can lead to cell transformation or death. The budding yeast MMS1 and MMS22 genes were identified in a screen for mutants that were hypersensitive to DNA alkylation that blocks replisome progression. I set out to investigate …
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A Pan-Cancer Single-Cell Analysis of Intratumoral Copy Number Diversity and Evolution
… evolution (PCNE), a short period of transient genome instability led to the generation of many tumor subclones (7-22) that grouped into 3-5 major superclones.</p> <p>We then extended the application of ACT to a pan-cancer study involving 94 tumors across seven major cancer types: bladder, …
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Establishing DNA combing to investigate DNA replication stress in vitro
… each daughter cell a complete copy of the genome. Replication proceeds bi-directionally from a minority of potential origins licensed for replication by a variety of replication factor proteins. Replication is catalysed by processive replication enzymes known as DNA polymerases and is …
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Investigating the role of protein ubiquitylation in the maintenance of genome stability
… (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 hallmark of HR-deficient cells, namely synthetic lethality with the …
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Functional investigation of the role of the retinoblastoma protein in genome stability
Genome instability is an enabling characteristic of cancerous cells. It has recently been discovered that the retinoblastoma protein (pRB), typically known for its role in cell cycle regulation, also aids in the maintenance of genome stability. Intriguingly, mutations to the pRB gene, RB1, can …
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