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 18 of 18 for “"telomere dysfunction"”.
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Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract
… of CIN in cancer is the improper repair of dysfunctional telomeres. Telomeres comprise the linear ends of chromosomes and play a dual role in cancer. Its length is maintained by the ribonucleoprotein, telomerase, which is not a normally expressed in somatic cells and as cells divide, …
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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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Telomeric Regulation of Chromosomal Instability In Colorectal Cancer
<p>Telomere dysfunction drives chromosomal instability (CIN) during the transition from benign adenoma to malignant adenocarcinoma. While CIN provides a mutator mechanism for cancer-relevant genomic events, its role in shaping tumor biology during carcinogenesis is not well understood. Here, we …
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Flap Endonuclease 1 ensures telomere replication and stability
Telomeres, protein-DNA structures that distinguish the end of a chromosome from a bona fide DNA double strand break, are integral to genomic stability. High fidelity replication of telomeres is indispensable for their stability. Telomere replication is a challenging task that is completed through …
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Causes and Consequences of Genomic Instability in Prostatic Carcinogenesis
… candidates for the cause of these alterations, telomere dysfunction is thought to be a major contributor. Telomeres are the terminal ends of human chromosomes, and when dysfunctional can lead to break-fusion-bridge cycles and multi-polar mitoses that generate numerical and structural chromosomal …
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Further Insight into the Two Functions of Telomeres: Determining the Role of Tankyrase1 in Telomere Length Regulation and Tin2 in Telomere Protection
… poly(ADP-ribose) polymerase that can localize to telomeres through its interaction with the shelterin component TRF1. Tankyrase1 poly(ADP-ribosyl)ates TRF1 in vitro, and its nuclear overexpression leads to loss of TRF1 and telomere elongation, suggesting that tankyrase1 is a positive regulator of …
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Dissecting the Role of ATRX in Soft Tissue Sarcoma Development and Therapeutic Response
… sarcomas have increased persistent DNA damage, telomere dysfunction, and mitotic catastrophe. We find that Atrx deleted tumors have impaired cGAS-STING signaling, with accompanying sensitivity to the novel clinical therapy oncolytic herpesvirus. Translation of these results to patients with ATRX …
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Preclinical evaluation of a novel telomerase inhibitor in malignant cells of the hematopoietic system
… for the inhibition of telomerase resulting in telomere dysfunction and delayed growth arrest in tumor cells. Here we examined the effects of BIBR1532 in different leukemia cell lines as well as in primary cells from patients with AML and CLL in short term culture assays. We observed a dose …
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Regulatio of actin cytoskeleton by TIS21 vi downregulating reactive oxygen species (ROS) in the doxorubicin-induced premature senescenc
… Cellular senescence is induced by DNA damage, telomere shortening or oncogene activation. During cellular senescence BTG2 is stabilized in response to telomere dysfunction. Doxorubicin is an effective anticancer drug that belongs to a class of anthracyclines and a commonly used inducer of DNA …
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The Apollo Nuclease Binds To TRF2 and Protects
… of enzymes, hSNM1B/Apollo, in complex with the telomere binding proteins TRF2/Rap1. Due to its low abundance at telomeres, we consider Apollo to be a telomere accessory factor, and not part of the core telomere protein complex, shelterin. Apollo localizes to telomeres by interacting directly …
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ONCOGENE-INDUCED ALTERED DNA REPLICATION DYNAMICS
… stress mainly at fragile sites and since telomeres resemble fragile sites, I then demonstrated that oncogene activation impairs telomere replication, by increasing fork stalling at telomeres. This is accompanied by increased fragile telomeres, stochastic telomeric attrition and persistent …
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Telomere-Driven Tetraploidy and its Relevance to Cancer
… of tetraploidization in cancer, originating from telomere dysfunction, a widespread phenomenon in early tumorigene sis. Prolonged telomere deprotection caused by inactivation of the telomeric proteins POT1a and POT1b leads to tetraploidy in p53/Rb de cient mouse cells. Irreversible telomere …
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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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The Role of Pot1 in Telomere Protection and Maintenance
… telomeric DNA binding protein implicated in telomere length regulation in human cells. To address the role of POT1 in telomere protection we used RNAi in human cells. We confirmed that POT1 acts as a negative regulator of telomerase and showed that POT1 is required to protect telomeres. …
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A Novel Phosphorylation Site in the Telomeric Protein TRF2 is Regulated by the ATR Kinase and Plays a Role in Relieving Replication Stress at the Telomere
… (PIKKs) have a well documented function at yeast telomeres. Although several lines of evidence suggest that members of the PIKK family also play a role in vertebrate telomere biology, little is known about their specific functions. We report that the human shelterin component, TRF2, overexpressed …
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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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Drivers of melanoma susceptibility
… these analyses suggested that genes regulating telomere function could be influencing melanoma risk. After performing functional experimental analyses, our research team was able to determine that carriers of rare variants in the protection of telomeres (POT1) gene, a member of the shelterin …
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Investigation of a pancreatic derived progenitor cell population for use in regenerative medicine
… can be induced by multiple factors, including telomere dysfunction associated with replication and oxidant stress. Senescence of stem cell, or progenitor, populations has been proposed as a factor in impaired tissue homeostasis and a mechanism of ageing. In addition, cellular senescence may be …