scholarly journals Mathematical model identifies effective P53 accumulation with target gene binding affinity in DNA damage response for cell fate decision

Cell Cycle ◽  
2018 ◽  
Vol 17 (24) ◽  
pp. 2716-2730 ◽  
Author(s):  
Tingzhe Sun ◽  
Dan Mu ◽  
Jun Cui
Keyword(s):  
Mathematical Model ◽  
Dna Damage ◽  
Cell Fate ◽  
Binding Affinity ◽  
Dna Damage Response ◽  
Target Gene ◽  
Cell Fate Decision ◽  
Damage Response ◽  
Fate Decision

scholarly journals Autophagy Roles in Genome Maintenance

Cancers ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 1793 ◽  
Author(s):  
Susanna Ambrosio ◽  
Barbara Majello
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Current Knowledge ◽  
Response To Therapy ◽  
Genome Integrity ◽  
Genome Maintenance ◽  
Damage Response ◽  
Cancer Cell Survival ◽  
Fate Decision

In recent years, a considerable correlation has emerged between autophagy and genome integrity. A range of mechanisms appear to be involved where autophagy participates in preventing genomic instability, as well as in DNA damage response and cell fate decision. These initial findings have attracted particular attention in the context of malignancy; however, the crosstalk between autophagy and DNA damage response is just beginning to be explored and key questions remain that need to be addressed, to move this area of research forward and illuminate the overall consequence of targeting this process in human therapies. Here we present current knowledge on the complex crosstalk between autophagy and genome integrity and discuss its implications for cancer cell survival and response to therapy.

scholarly journals Tau affects P53 function and cell fate during the DNA damage response

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Martina Sola ◽  
Claudia Magrin ◽  
Giona Pedrioli ◽  
Sandra Pinton ◽  
Agnese Salvadè ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Neurodegenerative Disorder ◽  
Neuroblastoma Cells ◽  
Molecular Response ◽  
Loss Of Function ◽  
Protein Deposition ◽  
Medical Need ◽  
Damage Response ◽  
Fate Decision

Abstract Cells are constantly exposed to DNA damaging insults. To protect the organism, cells developed a complex molecular response coordinated by P53, the master regulator of DNA repair, cell division and cell fate. DNA damage accumulation and abnormal cell fate decision may represent a pathomechanism shared by aging-associated disorders such as cancer and neurodegeneration. Here, we examined this hypothesis in the context of tauopathies, a neurodegenerative disorder group characterized by Tau protein deposition. For this, the response to an acute DNA damage was studied in neuroblastoma cells with depleted Tau, as a model of loss-of-function. Under these conditions, altered P53 stability and activity result in reduced cell death and increased cell senescence. This newly discovered function of Tau involves abnormal modification of P53 and its E3 ubiquitin ligase MDM2. Considering the medical need with vast social implications caused by neurodegeneration and cancer, our study may reform our approach to disease-modifying therapies.

scholarly journals Cellular responses to a prolonged delay in mitosis are determined by a DNA damage response controlled by Bcl-2 family proteins

Open Biology ◽  
2015 ◽  
Vol 5 (3) ◽  
pp. 140156 ◽  
Author(s):  
Didier J. Colin ◽  
Karolina O. Hain ◽  
Lindsey A. Allan ◽  
Paul R. Clarke
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Protein Kinases ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Cell Cycle Progression ◽  
Cycle Progression ◽  
Anti Cancer ◽  
Damage Response ◽  
Microtubule Poisons

Anti-cancer drugs that disrupt mitosis inhibit cell proliferation and induce apoptosis, although the mechanisms of these responses are poorly understood. Here, we characterize a mitotic stress response that determines cell fate in response to microtubule poisons. We show that mitotic arrest induced by these drugs produces a temporally controlled DNA damage response (DDR) characterized by the caspase-dependent formation of γH2AX foci in non-apoptotic cells. Following exit from a delayed mitosis, this initial response results in activation of DDR protein kinases, phosphorylation of the tumour suppressor p53 and a delay in subsequent cell cycle progression. We show that this response is controlled by Mcl-1, a regulator of caspase activation that becomes degraded during mitotic arrest. Chemical inhibition of Mcl-1 and the related proteins Bcl-2 and Bcl-x L by a BH3 mimetic enhances the mitotic DDR, promotes p53 activation and inhibits subsequent cell cycle progression. We also show that inhibitors of DDR protein kinases as well as BH3 mimetics promote apoptosis synergistically with taxol (paclitaxel) in a variety of cancer cell lines. Our work demonstrates the role of mitotic DNA damage responses in determining cell fate in response to microtubule poisons and BH3 mimetics, providing a rationale for anti-cancer combination chemotherapies.

c-ABL tyrosine kinase modulates p53-dependent p21 induction and ensuing cell fate decision in response to DNA damage

2014 ◽  
Vol 26 (2) ◽  
pp. 444-452 ◽  
Author(s):  
S.M. Nashir Udden ◽  
Yuiko Morita-Fujimura ◽  
Masanobu Satake ◽  
Shuntaro Ikawa
Keyword(s):  
Dna Damage ◽  
Tyrosine Kinase ◽  
Cell Fate ◽  
Cell Fate Decision ◽  
Abl Tyrosine Kinase ◽  
Fate Decision

scholarly journals Modulation of the E2F1-Driven Cancer Cell Fate by the DNA Damage Response Machinery and Potential Novel E2F1 Targets in Osteosarcomas

2009 ◽  
Vol 175 (1) ◽  
pp. 376-391 ◽  
Author(s):  
Michalis Liontos ◽  
Katerina Niforou ◽  
Georgia Velimezi ◽  
Konstantinos Vougas ◽  
Konstantinos Evangelou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Cancer Cell ◽  
Dna Damage Response ◽  
Damage Response

scholarly journals p53 dynamics orchestrates with binding affinity to target genes for cell fate decision

2017 ◽  
Vol 8 (10) ◽  
pp. e3130-e3130 ◽  
Author(s):  
Mengqiu Wu ◽  
Hui Ye ◽  
Zhiyuan Tang ◽  
Chang Shao ◽  
Gaoyuan Lu ◽  
...  
Keyword(s):  
Cell Fate ◽  
Binding Affinity ◽  
Target Genes ◽  
Cell Fate Decision ◽  
Fate Decision

scholarly journals Autophagic Organelles in DNA Damage Response

2021 ◽  
Vol 9 ◽  
Author(s):  
Jeongha Kim ◽  
Sungmin Lee ◽  
Hyunwoo Kim ◽  
Haksoo Lee ◽  
Ki Moon Seong ◽  
...  
Keyword(s):  
Dna Damage ◽  
Cell Fate ◽  
Dna Damage Response ◽  
Cellular Homeostasis ◽  
Dna Damaging Agents ◽  
Anti Cancer ◽  
Damage Response ◽  
Cargo Proteins ◽  
Cellular Stresses ◽  
Key Events

Autophagy is an important subcellular event engaged in the maintenance of cellular homeostasis via the degradation of cargo proteins and malfunctioning organelles. In response to cellular stresses, like nutrient deprivation, infection, and DNA damaging agents, autophagy is activated to reduce the damage and restore cellular homeostasis. One of the responses to cellular stresses is the DNA damage response (DDR), the intracellular pathway that senses and repairs damaged DNA. Proper regulation of these pathways is crucial for preventing diseases. The involvement of autophagy in the repair and elimination of DNA aberrations is essential for cell survival and recovery to normal conditions, highlighting the importance of autophagy in the resolution of cell fate. In this review, we summarized the latest information about autophagic recycling of mitochondria, endoplasmic reticulum (ER), and ribosomes (called mitophagy, ER-phagy, and ribophagy, respectively) in response to DNA damage. In addition, we have described the key events necessary for a comprehensive understanding of autophagy signaling networks. Finally, we have highlighted the importance of the autophagy activated by DDR and appropriate regulation of autophagic organelles, suggesting insights for future studies. Especially, DDR from DNA damaging agents including ionizing radiation (IR) or anti-cancer drugs, induces damage to subcellular organelles and autophagy is the key mechanism for removing impaired organelles.

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