Oscillatory Behaviors of Delayed p53 Regulatory Network with microRNA 192 in DNA Damage Response

2021 ◽  
Vol 31 (02) ◽  
pp. 2150020
Author(s):  
Chunyan Gao ◽  
Fangqi Chen
Keyword(s):  
Dna Damage ◽  
Time Delay ◽  
Dna Damage Response ◽  
Positive Feedback ◽  
Regulatory Network ◽  
Feedback Loop ◽  
Research Work ◽  
Positive Feedback Loop ◽  
Damage Response ◽  
High Level

This study develops a general model of delayed p53 regulatory network in the DNA damage response by introducing microRNA 192-mediated positive feedback loop based on the existing research work. Through theoretical analysis and numerical simulation, we find that the delay as a bifurcation parameter can drive the p53-Mdm2 module to undergo a supercritical Hopf bifurcation, thereby producing oscillation behavior. Moreover, we demonstrate how the positive feedback loop formed by p53* and microRNA 192 (miR-192) with the feature of double-negative regulation produces oscillations. Further, a comparison is given to demonstrate that microRNA 192-mediated positive feedback loop affects the robustness of system oscillations. In addition, we show that ataxia telangiectasia mutated kinase (ATM), once activated by DNA damage, makes p53* undergo two Hopf bifurcations. These results reveal that both time delay and miR-192 play tumor suppressing roles by promoting p53 oscillation or high level expression, which will provide a perspective for promoting the development of anti-cancer drugs by targeting miR-192 and time delay.

scholarly journals USP49 participates in the DNA damage response by forming a positive feedback loop with p53

2018 ◽  
Vol 9 (5) ◽  
Author(s):  
Rongfu Tu ◽  
Wenqian Kang ◽  
Xuefei Yang ◽  
Qi Zhang ◽  
Xiaoyu Xie ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Positive Feedback Loop ◽  
Damage Response

scholarly journals ZNF506-dependent positive feedback loop regulates H2AX signaling after DNA damage

2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Somaira Nowsheen ◽  
Khaled Aziz ◽  
Kuntian Luo ◽  
Min Deng ◽  
Bo Qin ◽  
...  
Keyword(s):  
Dna Damage ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Positive Feedback Loop

scholarly journals trans-Fatty acids facilitate DNA damage-induced apoptosis through the mitochondrial JNK-Sab-ROS positive feedback loop

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yusuke Hirata ◽  
Aya Inoue ◽  
Saki Suzuki ◽  
Miki Takahashi ◽  
Ryosuke Matsui ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Dna Damage ◽  
Positive Feedback ◽  
Trans Fatty Acids ◽  
Feedback Loop ◽  
Positive Feedback Loop ◽  
Induced Apoptosis

scholarly journals Dynamic Behavior of p53 Driven by Delay and a Microrna-34a-Mediated Feedback Loop

2020 ◽  
Vol 21 (4) ◽  
pp. 1271 ◽  
Author(s):  
Chunyan Gao ◽  
Haihong Liu ◽  
Fang Yan
Keyword(s):  
Dna Damage ◽  
Hopf Bifurcation ◽  
Time Delay ◽  
Feedback Loop ◽  
Acute Stress ◽  
Oscillatory Dynamics ◽  
P53 Signaling ◽  
Anti Cancer ◽  
High Level ◽  
P53 Signaling Pathway

The tumor suppressor protein p53 is a critical hub in the comprehensive transcriptional network that inhibits the growth of cells after acute stress stimulation. In this paper, an integrated model of the p53 signaling pathway in response to DNA damage is proposed and the p53 stability and oscillatory dynamics are analyzed. Through theoretical analysis and numerical simulation, we find that the delay as a bifurcation parameter can drive the p53-Mdm2 module to undergo a supercritical Hopf bifurcation, thereby producing oscillation behavior. Moreover, we demonstrate how the positive feedback loop formed by p53* and microRNA-34a (miR-34a) with the feature of double-negative regulation produces limit-cycle oscillations. Further, we find that miR-34a can affect the critical value of Hopf bifurcation in delay-induced p53 networks. In addition, we show that ATM, once activated by DNA damage, makes p53* undergo two Hopf bifurcations. These results revealed that both time delay and miR-34a can have tumor suppressing roles by promoting p53 oscillation or high level expression, which will provide a perspective for promoting the development of anti-cancer drugs by targeting miR-34a and time delay.

scholarly journals Micronucleus Production, Activation of DNA Damage Response and cGAS-STING Signaling in Syncytia Induced by SARS-CoV-2 Infection

2021 ◽  
Author(s):  
He Ren ◽  
Chaobing Ma ◽  
Haoran Peng ◽  
Bo Zhang ◽  
Lulin Zhou ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Immune Activation ◽  
Target Genes ◽  
Average Rate ◽  
Downstream Target ◽  
Damage Response ◽  
Underlying Mechanisms ◽  
High Level ◽  
Syncytia Formation

Abstract SARS-CoV-2 infection could cause severe acute respiratory syndrome, largely attributed to dysregulated immune activation and extensive lung tissue damage. However, the underlying mechanisms are not fully understood. Here, we reported that viral infection could induce syncytia formation within cells expressing ACE2 and the SARS-CoV-2 spike protein, leading to the production of micronuclei with an average rate of about 4 per syncytium (> 93%). Remarkably, these micronuclei were manifested with a high level of activation of both DNA damage response and cGAS -STING signaling, as indicated by micronucleus translocation of gH2Ax and cGAS, and upregulation of their respective downstream target genes. Since activation of these signaling pathways were known to be associated with cellular catastrophe and aberrant immune activation, these findings help explain the pathological effects of SARS-CoV-2 infection at cellular and molecular levels, and provide novel potential targets for COVID-19 therapy.

scholarly journals Deciphering the Genetic Aberrations in DNA Damage Response Genes and Their Possible Association with HNSCC

2020 ◽  
pp. 156-169
Author(s):  
L. Akshayaa ◽  
A. S. Smiline Girija ◽  
A. Paramasivam ◽  
J. Vijayashree Priyadharsini
Keyword(s):  
Dna Damage ◽  
Dna Damage Response ◽  
Wide Spectrum ◽  
Survival Curve ◽  
Cell Cycle Checkpoint ◽  
Single Nucleotide Variants ◽  
Differential Expression Pattern ◽  
Damage Response ◽  
Cycle Checkpoint ◽  
High Level

Head and neck squamous cell carcinoma (HNSCC) includes carcinomas in the oral cavity, pharynx and larynx. It is considered as the sixth most common form of cancer in the world. Several studies have confirmed that smoking and alcohol consumption are the major risk factors for HNSCC. DNA damage response genes play an important role in the maintenance of the genome. Defects in cell cycle checkpoint and DNA repair mechanisms, such as mutation or abnormalities, may lead to the wide spectrum of human diseases. The present study employs databases and computational tools to identify the genetic abnormalities associated with DNA damage related genes which might have a direct or indirect association with HNSCC. The demographic details of HNSCC patients was obtained from The Cancer Gene Atlas (TCGA, Firehose Legacy) dataset hosted by the cBioportal database. The oncoprint data analysis revealed the highest frequency of gene alteration in the ATR gene (15%), followed by ATM, BRCA2 and CHEK2 (5%). Other genes showed less than 5% alteration. The gene expression profile of ATR gene revealed its differential expression pattern in different grades of tumor relative to normal samples. The survival curve analysis using Kaplan-Meier method revealed that a high level expression of the ATR gene leads to poor survival rate in the female HNSCC patients when compared to males. Thus the present study has identified gross and single nucleotide variants in the ATR gene which could have a putative role in the development of tumor. Further experimental research is required to confirm this association.

scholarly journals TNFα-senescence initiates a STAT-dependent positive feedback loop, leading to a sustained interferon signature, DNA damage, and cytokine secretion

Aging ◽  
2017 ◽  
Vol 9 (11) ◽  
pp. 2411-2435 ◽  
Author(s):  
Renuka Kandhaya-Pillai ◽  
Francesc Miro-Mur ◽  
Jaume Alijotas-Reig ◽  
Tamara Tchkonia ◽  
James L. Kirkland ◽  
...  
Keyword(s):  
Dna Damage ◽  
Positive Feedback ◽  
Feedback Loop ◽  
Cytokine Secretion ◽  
Positive Feedback Loop ◽  
Interferon Signature
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