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 17 of 17 for “"Pot1"”.
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Distinct functions of POT1 at telomeres.
… least well characterized of these proteins is POT1. POT1 binds telomeric ssDNA via a pair of Nterminal OB‐folds. Through its C‐terminal protein‐interaction domain, POT1 directly binds the telomeric dsDNA‐binding protein TRF2 and participates in heterodimeric complex with the protein TPP1. …
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The Role of Pot1 in Telomere Protection and Maintenance
<p>POT1 is a single stranded 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 …
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Distinct Functions of POT1 in Telomere Protection and Length Regulation
… and telomerase access. The mammalian protein POT1 binds to telomeric single-stranded DNA (ssDNA), protecting chromosome ends from being detected as sites of DNA damage and negatively regulating telomere length. POT1 is composed of an N-terminal ssDNA-binding domain and a C-terminal …
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Cell cycle-dependent modification of Pot1 and its effects on telomere function
… phosphorylates the telomere binding protein Pot1, and that this phosphorylation is crucial for DNA 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 …
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Investigating Mechanisms of Telomere End-Protection
… exist. Targeting of human shelterin component POT1 (POT1a/b in the mouse) with shRNAs shows a reduction in 3' telomere overhangs and a mild induction of DNA damage signaling. However, deletion of mouse POT1a and –b results in extended 3' overhangs and a massive induction of the DNA damage …
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On the Second Telomere Maintenance Machine: Structure, Recruitment, and Regulation of the CST–Polα/primase C-strand Fill-in Complex
… in CST,and in one case, the shelterin subunit POT1.This thesis provides a molecular basis for the pathogenesis of a subset of these CP mutations.In Chapter 2,I set out to determine the structure of CST–Polα/primase using cryogenic electron microscopy (cryo-EM), a state-of-the-art structural …
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Drivers of melanoma susceptibility
… of rare variants in the protection of telomeres (POT1) gene, a member of the shelterin complex that safeguards telomere integrity, are at high risk for developing melanoma. We successfully described the mechanism by which this happens, showing that the variants identified either disrupt POT1 mRNA …
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Biochemical and structural studies of human telomerase regulation
… a heterodimer with another shelterin component POT1 (Xin et al., 2007). After synthesizing approximately 60 telomeric repeats, telomerase is terminated by a CST (CTC1-STN1-TEN1) complex (Feng et al., 2018). In my thesis, I describe the biochemical and structural work aimed at understanding the …
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Effect of oxidative stress on human telomeric DNA structural dynamics and accessibility
… active binding of the protection of telomeres 1 (POT1) shelterin protein, suggesting enhanced accessibility of telomeric DNA to interacting molecules. The increased dynamics and accessibility caused by 8OG is comparable to the effect of a base substitution from G to C at the same position, which …
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Structural dynamics of telomeric overhang accessibility
… In addition, telomeric-binding proteins such as POT1 and TPP1 can sequester the overhang to regulate telomerase activity in vivo. Furthermore, existing small molecules that bind G-quadruplex have been shown to inhibit telomerase activity. However, there is little evidence on how the …
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Detection of Cell-free Tumor DNA in Liquid Biopsies of Dogs with B cell Lymphoma: A Biomarker Discovery
… were identified in cfDNA, including MYC, POT1, and TRAF3, alongside other cancer-related genes. Tumor samples showed mutations in genes associated with canine and human B-cell lymphoma. This study suggests that tumor-specific genomic mutations can be detected in plasma, supporting the …
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Identification of germline variants that predispose to familial melanoma
… mutations were found in CDKN2A, BRCA1, POT1 and BAP1. Disruptive variants were also observed in novel genes such as EXO5, TP53AIP and AMER1. An increased burden on variants in transcription factor binding motifs were observed in genes including SYK and SRC. A large deletion upstream of …
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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
… as a bridge linking TRF1 and TRF2 to TPP1 and POT1, the single-stranded telomeric DNA-binding protein. To gain further insight into the function of the TRF2-TIN2 complex, we created a TRF2 mutant that no longer associates with TIN2. Employing protein overlay assays, we established that TIN2 …
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Analysis of NEIL3 expression : a possible resistance factor to cancer chemotherapy in paediatric cancer cells
… these cells. Gene expression of NEIL3, hTERT and POT1 was measured by qRT-PCR in two cell lines of acute lymphoblastic leukaemia (ALL; steroid sensitive and steroid resistant cells), osteosarcoma, hepatoblastoma and medulloblastoma tumours. An initial assessment of whether the levels of NEIL3 …
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Replicative Senescence is ATM-Driven, Reversible, and Delayed by Reduced ATM Activity at Low Oxygen
… replicative senescence, raising the question of POT1 deficiency and subsequent ATR signaling. Moreover, low oxygen culture conditions impart an extension of fibroblast proliferative lifespan, indicating the nature of the critically-short telomere, or the response to that telomere, may be …
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Mechanisms of Telomere End Protection by TRF2
… subunits of shelterin, TRF1, TRF2, TIN2, TPP1, POT1, and Rap1, each have distinct roles in telomere homeostasis. These include telomere length regulation and preventing telomeres from activating various DNA damage response (DDR) signaling and double-strand break repair pathways. The need to …
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Modeling Sporadic Tumor Formation Driven By Telomere Dysfunction In The Gastrointestinal Tract
… proteins that bind to telomeres specifically. Pot1a is a highly conserved member of this complex that specifically binds to the telomeric single-stranded 3’ G-rich overhang. Previous work in our lab has shown that Pot1a is essential for chromosomal end protection as deletion of Pot1a in murine …