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 9 of 9 for “"Alternative lengthening of telomeres"”.
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Telomere Specific Homologous Recombination in the Alternative Lengthening of Telomeres
Over twenty years have passed since the discovery of telomerase-independent telomere maintenance, yet the precise details of the ALT mechanism remain a mystery. A growing body of evidence suggests that ALT cells maintain telomeres by homologous recombination (Reddel 2003 for Review). Groundbreaking …
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Role of ORCA/LRWD1 in the maintenance of telomere integrity
Telomeres are defined as the repetitive sequences at the end of linear chromosomes. The loss of telomere integrity leads to genome instability. Telomere integrity is maintained by the coordination of replication, heterochromatin, and DNA damage repair machinery. In this thesis, I describe how …
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Cell cycle-dependent modification of Pot1 and its effects on telomere function
… damage checkpoint inactivation, the suppression of homologous recombination (HR) at telomeres, and the prevention of telomere loss. DDK phosphorylates Pot1 in a very conserved region of its most amino-terminal-proximal OB fold, suggesting that this regulation of telomere function may be widely …
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Comprehensive Integrated Genomic and Histopathological Analysis of Paediatric Diffuse Intrinsic Pontine Glioma
… radiation alone. Although the delicate location of these lesions is a contributing factor to the dismal outcomes seen in these children, most of these clinical trials were designed based on adult protocols, with assumptions that paediatric brainstem tumours, whose histology most often resembles …
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Investigating the roles of lncRNA TERRA in telomerase-to-ALT transition using cancer cell lines and multicellular organisms
Telomeres protect eukaryotic chromosomes from fusions and degradations and progressively shorten over generations due to the “end replication problem” in human somatic cells, leading to cell cycle arrest, senescence and ultimately cell death. To achieve replicative immortality, tumors elongate …
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BETTING ON ALTERNATIVES: TARGETING TELOMERIC DILNCRNA AND BET PROTEINS IN ALT CANCER
The Alternative Lengthening of Telomeres (ALT) pathway is a homology-driven, damage-induced mechanism of telomere maintenance (TMM) that sustains the proliferation of 10-15% of human cancers. We have recently discovered that damaged DNA, including deprotected telomeres, triggers de novo …
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Functional Analysis of the Human SMC5/6 Complex in Homologous Recombination and Telomere Maintenance
… for the genomic stability and well-being of an organism. The structural maintenance of chromosomes (SMC) family of proteins has been implicated in the repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). The SMC1/3 cohesin complex promotes HR by localizing to DSBs …
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Mechanistic Understanding of the Role of TRF1 in Telomere Replication
<p>Mammalian telomeres are hard to replicate, and the shelterin subunit TRF1 is important for facilitating the replication of telomeric DNA. Deletion of TRF1 results in several phenotypes that are thought to be associated with telomere replication stress, including ATR signaling, fork stalling, …
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Characterizing and targeting the genomic consequences of ATRX deficiency in glioma
<p>Mutational inactivation of histone chaperone ATRX (a-thalassaemia/mental retardation X-linked) represents a defining molecular feature in several cancers, including malignant glioma. As standard of care only leads to transient responses and poor outcomes, there is an unmet clinical need for …