scholarly journals Phosphorylation of hRad17 by atr is Required for Cell Cycle Checkpoint Activation

2005 ◽  
Author(s):  
Wei Tan
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Activation ◽  
Cycle Checkpoint

scholarly journals Speedy/RINGO Regulation of CDKs in Cell Cycle, Checkpoint Activation and Apoptosis

Cell Cycle ◽  
2007 ◽  
Vol 6 (10) ◽  
pp. 1188-1193 ◽  
Author(s):  
Randy F. Gastwirt ◽  
Christopher W. McAndrew ◽  
Daniel J. Donoghue
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Checkpoint ◽  
Checkpoint Activation ◽  
Cycle Checkpoint

scholarly journals Heterogeneities in Cell Cycle Checkpoint Activation Following Doxorubicin Treatment Reveal Targetable Vulnerabilities in TP53 Mutated Ultra High-Risk Neuroblastoma Cell Lines

2021 ◽  
Vol 22 (7) ◽  
pp. 3664
Author(s):  
Linnéa Ödborn Jönsson ◽  
Maryam Sahi ◽  
Ximena Lopez-Lorenzo ◽  
Faye Leilah Keller ◽  
Ourania N. Kostopoulou ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Risk ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Cell Cycle Checkpoint ◽  
Cell Cycle Checkpoints ◽  
Dna Integrity ◽  
Checkpoint Activation ◽  
Ultra High Risk ◽  
Cycle Checkpoint

Most chemotherapeutics target DNA integrity and thereby trigger tumour cell death through activation of DNA damage responses that are tightly coupled to the cell cycle. Disturbances in cell cycle regulation can therefore lead to treatment resistance. Here, a comprehensive analysis of cell cycle checkpoint activation following doxorubicin (doxo) treatment was performed using flow cytometry, immunofluorescence and live-cell imaging in a panel of TP53 mutated ultra high-risk neuroblastoma (NB) cell lines, SK-N-DZ, Kelly, SK-N-AS, SK-N-FI, and BE(2)-C. Following treatment, a dose-dependent accumulation in either S- and/or G2/M-phase was observed. This coincided with a heterogeneous increase of cell cycle checkpoint proteins, i.e., phos-ATM, phos-CHK1, phos-CHK2, Wee1, p21Cip1/Waf1, and p27Kip among the cell lines. Combination treatment with doxo and a small-molecule inhibitor of ATM showed a delay in regrowth in SK-N-DZ, of CHK1 in BE(2)-C, of Wee1 in SK-N-FI and BE(2)-C, and of p21 in Kelly and BE(2)-C. Further investigation revealed, in all tested cell lines, a subset of cells arrested in mitosis, indicating independence on the intra-S- and/or G2/M-checkpoints. Taken together, we mapped distinct cell cycle checkpoints in ultra high-risk NB cell lines and identified checkpoint dependent and independent druggable targets.

scholarly journals Identifying Cell Cycle Modulators That Selectively Target ARID1A Deficiency Using High-Throughput Image-Based Screening

2017 ◽  
Vol 22 (7) ◽  
pp. 813-826
Author(s):  
Lihong Zhang ◽  
Jianfeng Shen ◽  
Yuping Yin ◽  
Yang Peng ◽  
Lulu Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
High Throughput ◽  
Cancer Therapeutics ◽  
Cell Cycle Checkpoint ◽  
Therapeutic Approaches ◽  
Checkpoint Activation ◽  
Evolutionarily Conserved ◽  
Cycle Checkpoint ◽  
Genomic Studies ◽  
High Throughput Assay

ARID1A, a component of the chromatin remodeling complex SWI/SNF, is an evolutionarily conserved complex that uses the energy of adenosine triphosphate hydrolysis to remodel chromatin structure and functions as a master regulator of gene transcription. Recent genomic studies have revealed that ARID1A is one of the most frequently mutated genes in human cancers. However, therapeutic approaches that selectively target ARID1A-mutant tumors are not yet clinically available. Our previous study showed that ARID1A facilitates chromatin response and cell cycle checkpoint activation after DNA damage. Therefore, an ARID1A deficiency may result in therapeutic vulnerabilities in cell cycle modulators. The goals of our study were to develop a novel screening approach, based on fluorescent ubiquitination-based cell cycle indicators (FUCCI), and to identify chemical agents that can selectively modulate the cell cycle transition in ARID1A-deficient cancer cells. Using this high-throughput assay, we screened 2643 compounds and identified six potential chemical modulators that can selectively modulate the cell cycle in ARID1A-deficient cells; these agents may be useful for developing new therapeutics for ARID1A-mutant tumors. In summary, our study demonstrates that FUCCI cell-based high-content screening is a powerful and effective approach for identifying cell cycle modulators and can be applied to multigenotypic screening for targeted cancer therapeutics.

scholarly journals WEE1 kinase inhibition reverses G2/M cell cycle checkpoint activation to sensitize cancer cells to immunotherapy

2018 ◽  
Vol 7 (10) ◽  
pp. e1488359 ◽  
Author(s):  
Lillian Sun ◽  
Ellen Moore ◽  
Rose Berman ◽  
Paul E. Clavijo ◽  
Anthony Saleh ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Cycle Checkpoint ◽  
M Cell ◽  
Checkpoint Activation ◽  
Kinase Inhibition ◽  
Cycle Checkpoint ◽  
Wee1 Kinase
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