Abstract 3877: An inhibitor-2 complex regulates cell cycle checkpoints in response to DNA damage

2010 ◽  
Author(s):  
Mianen Sun ◽  
Chenghe Lin ◽  
Xi Tang ◽  
Bo Xu
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Checkpoints

scholarly journals The transcription factors TFE3 and TFEB amplify p53 dependent transcriptional programs in response to DNA damage

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Eutteum Jeong ◽  
Owen A Brady ◽  
José A Martina ◽  
Mehdi Pirooznia ◽  
Ilker Tunc ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Transcription Factors ◽  
P53 Protein ◽  
Cell Cycle Control ◽  
Cell Cycle Checkpoints ◽  
Dependent Manner ◽  
Double Knockout ◽  
Protein Levels ◽  
Regulation Of Cell Cycle

The transcription factors TFE3 and TFEB cooperate to regulate autophagy induction and lysosome biogenesis in response to starvation. Here we demonstrate that DNA damage activates TFE3 and TFEB in a p53 and mTORC1 dependent manner. RNA-Seq analysis of TFEB/TFE3 double-knockout cells exposed to etoposide reveals a profound dysregulation of the DNA damage response, including upstream regulators and downstream p53 targets. TFE3 and TFEB contribute to sustain p53-dependent response by stabilizing p53 protein levels. In TFEB/TFE3 DKOs, p53 half-life is significantly decreased due to elevated Mdm2 levels. Transcriptional profiles of genes involved in lysosome membrane permeabilization and cell death pathways are dysregulated in TFEB/TFE3-depleted cells. Consequently, prolonged DNA damage results in impaired LMP and apoptosis induction. Finally, expression of multiple genes implicated in cell cycle control is altered in TFEB/TFE3 DKOs, revealing a previously unrecognized role of TFEB and TFE3 in the regulation of cell cycle checkpoints in response to stress.

scholarly journals DNA damage-induced cell cycle checkpoints and DNA strand break repair in development and tumorigenesis

Oncogene ◽  
1999 ◽  
Vol 18 (55) ◽  
pp. 7883-7899 ◽  
Author(s):  
Gopal K Dasika ◽  
Suh-Chin J Lin ◽  
Song Zhao ◽  
Patrick Sung ◽  
Alan Tomkinson ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Strand Break ◽  
Cell Cycle Checkpoints ◽  
Dna Strand Break ◽  
Break Repair ◽  
Dna Strand

DNA damage and cell cycle checkpoints in hyperoxic lung injury: braking to facilitate repair

2001 ◽  
Vol 281 (2) ◽  
pp. L291-L305 ◽  
Author(s):  
Michael A. O'Reilly
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Genotoxic Stress ◽  
Supplemental Oxygen ◽  
Cell Cycle Checkpoints ◽  
Dna Integrity ◽  
Additional Time ◽  
Pulmonary Response ◽  
Arterial Blood ◽  
Hyperoxic Lung Injury

The beneficial use of supplemental oxygen therapies to increase arterial blood oxygen levels and reduce tissue hypoxia is offset by the knowledge that it injures and kills cells, resulting in increased morbidity and mortality. Although many studies have focused on understanding how hyperoxia kills cells, recent findings reveal that it also inhibits proliferation through activation of cell cycle checkpoints rather than through overt cytotoxicity. Cell cycle checkpoints are thought to be protective because they allow additional time for injured cells to repair damaged DNA and other essential molecules. During recovery in room air, the lung undergoes a burst of proliferation to replace injured and dead cells. Failure to terminate this proliferation has been associated with fibrosis. These observations suggest that growth-suppressive signals, which inhibit proliferation of injured cells and terminate proliferation when tissue repair has been completed, may play an important role in the pulmonary response to hyperoxia. Because DNA replication is coupled with DNA repair, activation of cell cycle checkpoints during hyperoxia may be a mechanism by which cells protect themselves from oxidant genotoxic stress. This review examines the effect of hyperoxia on DNA integrity, pulmonary cell proliferation, and cell cycle checkpoints activated by DNA damage.

scholarly journals A kinetochore-based ATM/ATR-independent DNA damage checkpoint maintains genomic integrity in trypanosomes

2019 ◽  
Vol 47 (15) ◽  
pp. 7973-7988 ◽  
Author(s):  
Qing Zhou ◽  
Kieu T M Pham ◽  
Huiqing Hu ◽  
Yasuhiro Kurasawa ◽  
Ziyin Li
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Spindle Assembly Checkpoint ◽  
Cell Cycle Checkpoint ◽  
Cell Cycle Checkpoints ◽  
Genomic Integrity ◽  
Metaphase Arrest ◽  
M Cell ◽  
Independent Manner ◽  
Mitotic Cyclin

Abstract DNA damage-induced cell cycle checkpoints serve as surveillance mechanisms to maintain genomic stability, and are regulated by ATM/ATR-mediated signaling pathways that are conserved from yeast to humans. Trypanosoma brucei, an early divergent microbial eukaryote, lacks key components of the conventional DNA damage-induced G2/M cell cycle checkpoint and the spindle assembly checkpoint, and nothing is known about how T. brucei controls its cell cycle checkpoints. Here we discover a kinetochore-based, DNA damage-induced metaphase checkpoint in T. brucei. MMS-induced DNA damage triggers a metaphase arrest by modulating the abundance of the outer kinetochore protein KKIP5 in an Aurora B kinase- and kinetochore-dependent, but ATM/ATR-independent manner. Overexpression of KKIP5 arrests cells at metaphase through stabilizing the mitotic cyclin CYC6 and the cohesin subunit SCC1, mimicking DNA damage-induced metaphase arrest, whereas depletion of KKIP5 alleviates the DNA damage-induced metaphase arrest and causes chromosome mis-segregation and aneuploidy. These findings suggest that trypanosomes employ a novel DNA damage-induced metaphase checkpoint to maintain genomic integrity.

An intimate alliance of DNA-damage response network with cell-cycle checkpoints amid events of uncontrolled cellular proliferation- a mini review

2020 ◽  
Author(s):  
Rajni Khan
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Dna Damage Response ◽  
Cellular Proliferation ◽  
Signal Transmission ◽  
Cell Senescence ◽  
Effector Proteins ◽  
Cell Cycle Checkpoints ◽  
Response Network ◽  
Damage Response

There is a close interdependence between the cell survival, cell senescence, events of cell cycle, apoptosis, malignancy development and tumor responses to cancer treatment. Intensive studies and elaborate researches have been conducted on the functional aspects of oncogenes, tumor suppressor genes, apoptotic genes and members guiding cell cycle regulation. These disquisitions have put forward the existence of a highly organized response pathway termed as DNA-damage response network. The pathways detecting DNA damage and signaling are intensively linked to the events of cell-cycle arrest, cell proliferation, apoptosis and cell senescence. DNA damage responses are complex systems that incorporate specific "sensor" and "transducer" proteins, for assessment of damage and signal transmission respectively. These signals are thereafter relayed upon various "effector" proteins involved in different cellular pathways. It may include those governing cell-cycle checkpoints, participating in DNA repair, cell senescence, and apoptosis.

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