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 14 of 14 for “"ATM kinase"”.
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Rational identification of a dual inhibitor of PARP-1 and ATM kinase
… gene) defects leading to successful patient treatment in ovarian, breast and prostate cancers. However, their use is limited to patients that harbour these BRCA1/2 defects. Beyond PARP inhibitors there are some DDR inhibitors currently in various phases of clinical trials, targeting: ATR …
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Development of Novel Technologies to Investigate DNA Double-Strand Break Repair Uncovers a Role for the ATM Kinase in Error-Free NHEJ with Implications for Neurodegenerative Diseases
… utilize an evolutionary conserved set of protein kinase signaling pathways that recognize and respond to DNA damage by pausing cell cycle progression and recruiting DNA repair machinery to ultimately determine the fidelity of DSB repair. Mutations and/or acquired defects that compromise the …
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The role of neuron-microglial interactions in Ataxia-Telangiectasia
… deficits. A-T is caused by mutations in ATM kinase, a critical regulator of cellular response to DNA damage, oxidative stress, and more broadly changes in homeostasis. Accumulating evidence indicates that dysregulated interactions between neurons and non-neuronal cell types, such as the …
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Identification and characterization of novel autoregulatory mechanism controlling ataxia telangiectasis mutated gene expression, protein traffiking and function
Ataxia-telangiectasia mutated gene product (ATM) is a 350 kDa Serine/Threonine kinase belonging to the family of Phosphatidylinositol-3 kinase like kinases. ATM functions as a key element in DNA Damage Response (DDR), a mechanism that maintains genomic integrity within the cells. ATM is activated …
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The Role of E2F1 In The Response to Dna Double Strand Breaks
… at serine 31 (serine 29 in mouse) by the ATM kinase as part of the DNA damage response. To investigate the importance of this event, our lab developed an E2F1 serine 29 mutant mouse model. I find that E2F1 serine 29 mutant cells show loss of E2F1 foci formation in response to DNA …
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Polyploidy and Mitotic Cell Death are Two Distinct HIV-1 Vpr-Driven Outcomes in Renal Tubule Epithelial Cells
… over time. Further, I identify a novel role for ATM kinase in promoting G2 arrest escape and polyploidy in this context. In summary, my work identifies ATM-dependent override of Vpr-mediated G2/M arrest as a critical determinant of cell fate Vpr+ RTECs. Further, our work highlights how a poorly …
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The interaction of CtIP with DNA damage response proteins
… signal transducer proteins such as the PIKK kinases ATM, ATR and SMG1 and the mediator proteins 53BP1 and MDC1. All of those proteins are involved in detecting and repairing double stranded or single stranded lesions. Moreover CtIP has a major influence on phosphorylation events induced …
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Identification and Characterization of the DNA Damage Response Function of Human Rif1 and a Search For Human Rap1 Interacting Factors
… other DNA damage response factors such as 53BP1, ATM, BRCA1, Chkl, Nbsl, and Rad 17. Furthermore, Rifl localized to uncapped telomeres, as do other DNA damage response factors. Among DNA damage response proteins, Rifl showed a unique dependence on the ATM kinase. Whereas inhibition of ATR …
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Mechanisms of cytosolic DNA sensing and neuroinflammation in ataxia-telangiectasia
… syndrome caused by loss-of-function mutations in ATM kinase, a master regulator of the cellular response to DNA damage, including DNA double stand breaks and oxidative stress. A-T is a multisystemic disease that manifests in the CNS as cerebellar degeneration, leading to debilitating ataxia. ATM …
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Replicative Senescence is ATM-Driven, Reversible, and Delayed by Reduced ATM Activity at Low Oxygen
… the nature of the activated DDR is unclear. ATM kinase activation at critically short telomeres has been implicated in the induction of senescence, suggesting that the shortest telomeres lack su]icient TRF2 to repress ATM signaling. However, ATM-deficient cells also undergo replicative …
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Role of NF-κB p65 subunit phosphorylation by ATM in DNA damage-regulated gene expression
… NF-κB activation requires activation of IκB kinase (IKK) complex, which phosphorylates IκBα, finally leading to its degradation. NF-κB transcription factor is then free to translocate to the nucleus where it regulates a wide array of target genes. NF-κB is an important regulator of diverse …
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How is Ataxia-Telangiectasia Mutated Protein Kinase Activated?
Ataxia-Telangiectasia Mutated (ATM) is a key protein kinase in the cell’s response to double-stranded breaks in DNA. This damage is detected by the Mre11-Rad50-Nbs1 (MRN) complex, which recruits ATM to the DNA. Upon activation, ATM phosphorylates a vast range of substrates, which triggers a …
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The Role of Adaptor Proteins in rDNA Double-Strand Break Repair by Homologous Recombination
… of the histone variant H2AX by the ATM kinase is dependent on Treacle and its two interaction partners TOPBP1 and NBS1, which together mediate mobilization of damaged rDNA repeats to the nucleolar periphery. The subsequent recruitment of the BRCA1-PALB2-BRCA2 complex occurs …
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Targeting the DNA damage response protein ATR kinase in pancreatic cancer
… with the implementation of personalised treatment strategies, has the potential to improve the poor survival outcomes of pancreatic ductal adenocarcinoma (PDAC). Many common genetic alterations in PDAC augment replication-associated DNA damage, or replication stress (RS), which increases …