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 10 of 10 for “"ATR kinase"”.
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Targeting the DNA damage response protein ATR kinase in pancreatic cancer
… factor, Ataxia Telangiectasia and Rad3-related (ATR) kinase. Furthermore, many chemotherapies used in the treatment of PDAC increase RS, leading to ATR activation which limits the efficacy of these therapies. Therefore, there is good rationale for targeting ATR as a strategy for treatment of …
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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
<p>Phosphatidyl inositol 3-kinase-like kinases (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 …
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THE ROLE OF INTERFERON REGULATORY FACTORS IN REGULATING THE EXPRESSION OF NKG2D LIGANDS
… to DNA damage depends on the serine/threonine kinase TBK1 and its phosphorylation target IRF3. The activation of IRF3 in response to DNA damage was evidenced by its phosphorylation and nuclear translocation. TBK1 is upstream of IRF3 and similarly, its phosphorylation was observed during DNA …
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Genome-wide CRISPR Screening in FBXW7-mutant Cells Uncovers Multiple Druggable Synthetic Lethal Interactions Involving Cell Cycle Control
… in increased sensitivity to an inhibitor of the ATR kinase - a mediator of the cellular response to replication stress. We hypothesize that activation of DNA damage response in FBXW7-/- cells leads to persistent ATR activation to mitigate replication stress and that ATR inhibition will force …
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Brit1/Mcph1 Mediates The Dna Damage Response By Inducing P53 Stability and Promoting Atr Signaling
… to sites of replication stress to maintain ATR signaling.</p> <p>The stability of p53 is largely dependent on its negative regulator, the MDM2 ubiquitin E3 ligase. Here, we provide evidence that in addition to its role as an upstream regulator of DNA damage response, BRIT1 is able to …
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ATR SIGNALING IN GENOME REPLICATION AND MAINTENANCE
… induced by these challenges activates the sensor kinase ATR in mammals (Mec1 in S. cerevisiae), which coordinates a multifaceted cellular response that is essential for maintaining genome integrity. Over the last few decades, ATR’s role in controlling the checkpoint upon the DNA damage response …
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DNA Damage-dependent Regulation and Function of akt-1 in Caenorhabditis elegans
… a single, conserved phosphatidylinositol 3-kinase (PI3K) signaling pathway that regulates somatic developmental decisions and lifespan through the Insulin-like receptor tyrosine kinase (RTK) DAF-2, the class I PI3K AGE-1 and the 3-phosphoinositide-dependent protein kinase 1 (PDK1) homologue …
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Neotelomere Formation by Telomerase in Human Cells
… We identify long-range DSB resection and ATR kinase signaling as repressors of telomerase at DSBs in human cells. Finally, we provide preliminary evidence that telomerase can synthesize a fully functional telomere de novo at a DSB. Our findings unveil a new function for telomerase in …
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Structural and Biochemical Investigation of Fanconi Anemia Pathway Activation
… structural tools. FANCI phosphorylation by the ATR DNA damage kinase stimulates D2-I ubiquitination in cells, which enables timely and coordinated FA pathway activation to ensure DNA repair fidelity. In this dissertation, I investigated the mechanism of this process by employing a …
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Understanding the activation mechanism of the Chk1 kinase
… DNA lesions promptly and efficiently. The ATR-Chk1 pathway is an essential component of the DDR, which is activated by single-strand DNA (ssDNA) generated as a result of DNA replication stress in S phase. Chk1 is a threonine/serine kinase that transduces the DNA damage signal and promotes …