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 27 for “"telomere maintenance"”.
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Biochemical analysis of proteins in the telomere maintenance pathway
… culminate in nucleoprotein structures designated telomeres. The terminal telomeric DNA consists of tandem repeats of a G-rich motif that is established and maintained by the action of the specialized reverse transcriptase called telomerase. In addition to the function of telomerase, the telomere …
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Functional Analysis of the Human SMC5/6 Complex in Homologous Recombination and Telomere Maintenance
… 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 where it holds sister chromatids …
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On the Second Telomere Maintenance Machine: Structure, Recruitment, and Regulation of the CST–Polα/primase C-strand Fill-in Complex
<p>Telomeres are the terminal nucleo protein components of eukaryotic chromosomes that safeguard genome integrity. Human telomeric DNA consists of double-stranded (ds) 5'-TTAGGG-3' repeats terminating in a 3' single-stranded (ss) overhang of the G-rich strand.The sequence and structure of the …
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Cell cycle-dependent modification of Pot1 and its effects on telomere function
Telomere functions are tightly controlled throughout the cell cycle to allow telomerase access while suppressing a bona fide DNA damage response (DDR) at linear chromosome ends. However, the mechanisms that link cell cycle progression with telomere functions are largely unknown. Here we show that a …
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Consequences of telomerase inhibition and telomere dysfunction in BRCA1 mutant cancer cells
Telomere maintenance is a critical component of genomic stability. An increasing body of evidence suggests BRCA1, a tumor suppressor gene with a variety of functions including DNA repair and cell cycle regulation, plays a role in telomere maintenance. Mutations in BRCA1 account for approximately …
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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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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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Sequence Effects and Ligand Selectivity in Targeting Non-Canonical DNA Structures
… in a wide range of processes including telomere maintenance, transcriptional control, and DNA replication and repair. In order to target specific G4 structures, and thus selectively affect these functions, improved small-molecule ligands are required. We have embarked on the synthesis of …
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Human telomerase reverse transcriptase (hTERT) overexpression modulates intracellular redox balance and protects cancer cells from apoptotic cell death
… to link hTERT to activities other than telomere maintenance and immortalization. Here we show that hTERT overexpression not only reduces the basal cellular ROS levels but also inhibits endogenous ROS production in response to stimuli that induce intracellular ROS generation. Conversely, …
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ZSCAN4 AND REPLICATION STRESS: SAFEGUARDING GENOME STABILITY IN MOUSE EMBRYONIC STEM CELLS
… plays a crucial role in mESC by contributing to telomere maintenance and genomic stability. Its prolonged knockdown leads to cell death, accompanied by karyotype abnormalities and telomere shortening. Moreover, deregulation of Zscan4 has been implicated in cancer development and maintenance. …
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Telomere Specific Homologous Recombination in the Alternative Lengthening of Telomeres
… 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 work by Oliver Bechter …
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The use of massively parallel sequencing to study the virome, epigenome and genome of canine and feline cancers
… in canine OSA, absence of genomic evidence of a telomere maintenance mechanism, recurrent shattering of chr26 in canine OSA and HSP90AB1, MITF and NOTCH2, as potentially actionable genes. These data will provide a significant resource for the community to generate new hypotheses and answer key …
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Clarifying the Role of the CST Complex in DNA Replication and Repair
… maintained by specialized structures known as telomeres. These structures are protected by a number of essential protein complexes including the shelterin complex and CST (CTC1 – STN1 – TEN1) complex. CST is an RPA-like ssDNA binding protein that is vital for telomere length maintenance via …
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Investigating the Molecular Mechanisms Underlying Ku Essentiality in Human Cells
… are not fully understood such as its roles in telomere maintenance, the cell cycle, and transcriptional regulation. Despite Ku’s conservation across mammalian species, Ku is essential for human cell viability but is dispensable in mice. Essentiality in human cells was previously suggested to be …
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Examination of molecular genetic factors involved in sensitivity to breast cancer following radiation exposure
… radiation exposure, DNA repair deficiency and telomere malfunction are associated with cancer risk, we investigated Lymphoblastoid Cell Lines (LCLs) from breast cancer patients and controls for chromosomal radiosensitivity, relative telomere length, and gene expression changes. The importance …
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Repression of telomerase components in isogenic normal, immortal and tumorigenic cells
The telomere maintenance enzyme telomerase is a ribonuclear protein complex that is active in 80-90% of immortal cancer cells. Three essential components of the active telomerase holoenzyme include the reverse transcriptase, hTERT, an RNA component (hTR) that has a template region for reverse …
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Functional Analysis of the Human Telomeric Protein TRF2
… human telomeric protein present at all telomeres throughout the cell cycle. TRF2 has been proposed remodel telomeres into large lasso-like structures named t-loops. Removal of TRF2 from telomeres by expression of a dominant negative allele of TRF2 (TRF2ΔBΔM) led dissolution of these …
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Molecular changes involved in oral cancer progression and their relevance to keratinocyte immortalisation
… immortalises D17 and this is associated with telomere lengthening but p53 remains wild-type. In contrast, transduction of hTERT does not extend the lifespan of two other typical mortal dyplasia cultures (that retain RAR-b and p16INK4a expression), even though telomeres are lengthened. Thus, …
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Unravelling TERRA regulation by the interplay of two mechanisms: RALY interaction and telomere-specific polyadenylation
… at chromosome ends which play key roles in telomere maintenance. TERRA transcripts are of variable length and sequence that is characterized by a subtelomere-specific portion at the 5’ end and a common portion with telomeric repeats at the 3’ end. TERRA is implicated in different aspects of …
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Role of hnRNP A1 in the Regulation of HDM2 Gene Expression
… hnRNP A1 extend to the processing of microRNAs, telomere maintenance and DNA repair 1. Our previous studies have shown that hnRNPA1 had reduced protein level and increased cytoplasmic accumulation in senescent human diploid fibroblasts 2,10. Our preliminary data showed that <em>HDM2</em> mRNA …
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