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 38 for “"Chk1"”.
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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 cell …
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Role of Chk1 and Chk2 in mitotic checkpoint control in vertebrate cells
Two conserved protein kinases, Chk1 and Chk2, are activated in response to genotoxic stress and mediate multiple cell cycle checkpoint mechanisms that ensure genomic integrity. The establishment of mitotic checkpoint delay in response to DNA damage or incompletely replicated DNA is conventionally …
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Loss of Chk1 Function and Exogenous Expression of Cyclin A1/Cdk2 Results in Apoptosis after the MBT in Early Xenopus laevis Embryos
… the role of two cell cycle components, Chk1 and cyclin A1/Cdk2, during apoptosis was studied during early development of Xenopus embryos. Chk1 is a serine/threonine kinase that inhibits the activity of cyclin-dependent kinases (Cdks) in response to unreplicated DNA. In the pre-MBT …
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Functions of RTF2 in DNA Replication and Checkpoint Control
… between RTF2 and checkpoint kinase 1 (CHK1), an essential kinase that functions downstream of ataxia-telangiectasia and Rad3-related (ATR) in the intrinsic S/G2 checkpoint, which we confirmed in cells. Remarkably, cells lacking RTF2 fail to recruit CHK1 to replication forks. Abrogation …
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Investigating Checkpoint Kinases 1/2 As Novel Therapeutic Targets In Head and Neck Squamous Cell Carcinoma
… targeted inhibition of checkpoint kinases Chk1/2 leads to cisplatin sensitization of p53-deficient cells through induction of mitotic death. Serendipitously, we also found out that a significant subset (roughly 20%) of HNSCC cell lines are acutely sensitive to single agent checkpoint …
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The Dynamics of the Unreplicated DNA Checkpoint in Xenopus laevis Embryos and Extracts
… of this study is the role of protein kinase Chk1 and the phosphatase Cdc25A in the DNA replication checkpoint. In the absence of active Chk1, Cdc25A activates cyclin dependent kinases (Cdks) allowing the cell to progress into S or M phase. Chk1 regulates cell cycle arrest in the presence of …
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Studies of Bioactive Natural Products and Mechanism-Based Bioassays
… for LCFA dereplication. The cell cycle kinase Chk1 is an interesting target for the development of agents which might potentiate DNA damaging agents. Typical assays for Chk1 involve the use of expensive or radioactive reagents. To facilitate the development of new assays using shorter peptide …
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Targeting transcription-regulating cyclin dependent kinase 12 for the treatment of breast cancer
… including inhibitors of PARP (olaparib) and CHK1 (AZD7762) using a colony formation assay. The preliminary results indicate that combining CDK12 and CHK1 inhibition will likely have greater therapeutic potential than the combination of CDK12 and PARP inhibition. Future studies are required to …
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DNA damage responses in the context of the cell division cycle
… functional interactions between Rad9 and Chk1 in S. cerevisiae. I show that specific consensus CDK sites within Rad9 N-terminus are essential to enable Chk1 phosphorylation and activation, and that MCPH1, a human homologue of Rad9, may share a conserved function in binding and activating …
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TARGETING THE DNA DAMAGE RESPONSE PATHWAY FOR THE TREATMENT OF AGGRESSIVE THYROID CANCERS, IN VITRO STUDIES
… also used to evaluate the effect of a selective Chk1 kinase inhibitor, Prexasertib (PX), currently employed in ongoing phase II clinical trials for other cancers treatment, which was used to treat cell lines either alone or in combination with DX or LENV. Flowcytometry analysis was used to …
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Prognostic and Treatment Predictive Markers Associated with Cyclin D1 Gene Amplification and Epithelial-Mesenchymal Transition in Breast Cancer
… were associated with CCND1 amplification (Chk1 and β-arrestin1), which has previously been linked to a potential adverse effect of tamoxifen, or with epithelial-mesenchymal transition (Snail), a biological process crucial for the development of metastasis. Immunohistochemical analyses of …
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Function of MCPH1 in Neurogenesis
… eine verminderte zentrosomale Lokalization von Chk1 in der G2-phase des Zellzyklus. Zentrosomal lokalisiertes Chk1 verhindert einen Eintritt in die Mitose durch temporäre negative Regulation von Cdc25B und Cdk1. Mcph1-defiziente Zellen aktivieren frühzeitig Cdk1 und leiten einen vorzeitigen …
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Biochemical and Molecular Characterisation of the FADDosome
… In part II, our group discovered that the ATR, Chk1 and Chk2 kinases are activated in 5-FU-treated HCT116 cells and play a key role in the 5-FU-induced DNA damage signal transduction towards caspase-10 upregulation and FADDosome formation. It was found that activation of Chk1 and Chk2 as well as …
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Roles for C-ABL and P53 in bone homeostasis and DNA damage response
… such as TopBP1, Brca1, activation of Chk2 and Chk1, phosphorylation of p53 at Ser15 and induction of p53 target genes, cell cycle checkpoints and DNA repair of ssDNA breaks. These findings were confirmed by c-Abl reconstitution. Further studies indicate that c-Abl functions upstream of Atm and …
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Investigation of The Roles of Asf1 and Caf-1-Mediated Chromatin Assembly In The Human Dna Damage Response
… and persistent activation of the ATR-Chk1 pathway. By contrast, ASF1 and CAF-1 render the rapid inactivation of ATM Chk2 pathway via facilitating histone acetylation to allow the recruitment of ATM to DSBs for efficient repair by non homologous end joining. Furthermore, in response to …
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Integration of the phosphorylation-dependent signaling in the DNA damage response network : implications for cancer
… kinase family that functions in parallel with CHK1 and CHK2 to integrate DNA damage signaling responses and cell cycle arrest in mammalian cells.
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Mismatch Repair Protein-Dependent Cytotoxic Signaling In Cells Treated With The Cancer Chemotherapeutic Cisplatin
… replicative stress respondents ATM, γH2AX and Chk1 occurs independently of MMR protein status upon treatment of cells with CDDP, suggesting that these proteins are not involved in CDDP-induced, MMR protein-dependent cytotoxic signaling. This study additionally reveals evidence for an MMR …
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Atr-Mediated Cd47 and Pd-L1 Upregulation Restricts Radiotherapy-Induced Immune Priming and Abscopal Responses In Colorectal Cancer
… a common DNA repair signaling pathway — ATR/Chk1/STAT3 — to upregulate both CD47 and PD-L1 in response to radiotherapy, which through engagement of SIRPα and PD-1 suppresses the capacity of antigen-presenting cells to phagocytose them thereby preventing TAA cross-presentation and innate …
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An investigation into the regulation of replication factories and dormant origins in human cells
… Cells also regulate replication factories in a Chk1-dependent manner in response to replicative stress. The combination of dormant origin activation and inhibition of replication factory activation helps ensure that the genome is fully replicated during S phase.<br/><br/>Using human tissue …
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The interaction of CtIP with DNA damage response proteins
… response pathways such as NBS1, ATM, 53BP1, Chk1 and RPA70. However, impaired phosphorylation only occurs in response to single stranded DNA lesions or the collapse of replication forks. This implies that it is the ATR pathway that is malfunctioning in CtIP depleted cells. CtIP was previously …
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