scholarly journals Evaluation of Cytotoxicity and DNA Damage Response with Analysis of Intracellular ATM Signaling Pathways

2014 ◽  
Vol 12 (5) ◽  
pp. 272-281 ◽  
Author(s):  
Sriram Bandi ◽  
Preeti Viswanathan ◽  
Sanjeev Gupta
Keyword(s):  
Dna Damage ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Damage Response ◽  
Atm Signaling

scholarly journals Avian Sarcoma and Leukosis Virus Cytopathic Effect in the Absence of TVB Death Domain Signaling

2005 ◽  
Vol 79 (13) ◽  
pp. 8243-8248 ◽  
Author(s):  
Sara Klucking ◽  
Asha S. Collins ◽  
John A. T. Young
Keyword(s):  
Dna Damage ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Cytopathic Effect ◽  
Tumor Necrosis Factor Receptor ◽  
Death Domain ◽  
Trail Receptors ◽  
Damage Response ◽  
Cellular Dna ◽  
Avian Sarcoma

ABSTRACT The cytopathic effect (CPE) seen with some subgroups of avian sarcoma and leukosis virus (ASLV) is associated with viral Env activation of the death-promoting activity of TVB (a tumor necrosis factor receptor-related receptor that is most closely related to mammalian TNF-related apoptosis-inducing ligand [TRAIL] receptors) and with viral superinfection leading to unintegrated viral DNA (UVD) accumulation, which is presumed to activate a cellular DNA damage response. In this study, we employed cells that express signaling-deficient ASLV receptors to demonstrate that an ASLV CPE can be uncoupled from the death-promoting functions of the TVB receptor. However, these cell-killing events were associated with much higher levels of viral superinfection and DNA accumulation than those seen when the virus used signaling-competent TVB receptors. These findings suggest that a putative cellular DNA damage response that is activated by UVD accumulation might act in concert with the death-signaling pathways activated by Env-TVB interactions to trigger cell death. Such a model is consistent with the well-established synergy that exists between TRAIL-signaling pathways and DNA damage responses which is currently being exploited in cancer therapy regimens.

scholarly journals Mutant huntingtin impairs PNKP and ATXN3, disrupting DNA repair and transcription

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Rui Gao ◽  
Anirban Chakraborty ◽  
Charlene Geater ◽  
Subrata Pradhan ◽  
Kara L Gordon ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Rna Polymerase Ii ◽  
Dna Damage Response ◽  
Functional Decline ◽  
Transcriptional Elongation ◽  
Damage Repair ◽  
Damage Response ◽  
Cyclic Amp Response Element ◽  
Atm Signaling

How huntingtin (HTT) triggers neurotoxicity in Huntington’s disease (HD) remains unclear. We report that HTT forms a transcription-coupled DNA repair (TCR) complex with RNA polymerase II subunit A (POLR2A), ataxin-3, the DNA repair enzyme polynucleotide-kinase-3'-phosphatase (PNKP), and cyclic AMP-response element-binding (CREB) protein (CBP). This complex senses and facilitates DNA damage repair during transcriptional elongation, but its functional integrity is impaired by mutant HTT. Abrogated PNKP activity results in persistent DNA break accumulation, preferentially in actively transcribed genes, and aberrant activation of DNA damage-response ataxia telangiectasia-mutated (ATM) signaling in HD transgenic mouse and cell models. A concomitant decrease in Ataxin-3 activity facilitates CBP ubiquitination and degradation, adversely impacting transcription and DNA repair. Increasing PNKP activity in mutant cells improves genome integrity and cell survival. These findings suggest a potential molecular mechanism of how mutant HTT activates DNA damage-response pro-degenerative pathways and impairs transcription, triggering neurotoxicity and functional decline in HD.

scholarly journals INTS3 controls the hSSB1-mediated DNA damage response

2009 ◽  
Vol 187 (1) ◽  
pp. 25-32 ◽  
Author(s):  
Jeffrey R. Skaar ◽  
Derek J. Richard ◽  
Anita Saraf ◽  
Alfredo Toschi ◽  
Emma Bolderson ◽  
...  
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Ataxia Telangiectasia ◽  
Binding Protein ◽  
Ataxia Telangiectasia Mutated ◽  
Uncharacterized Protein ◽  
Damage Response ◽  
Atm Signaling Pathway ◽  
Atm Signaling

Human SSB1 (single-stranded binding protein 1 [hSSB1]) was recently identified as a part of the ataxia telangiectasia mutated (ATM) signaling pathway. To investigate hSSB1 function, we performed tandem affinity purifications of hSSB1 mutants mimicking the unphosphorylated and ATM-phosphorylated states. Both hSSB1 mutants copurified a subset of Integrator complex subunits and the uncharacterized protein LOC58493/c9orf80 (henceforth minute INTS3/hSSB-associated element [MISE]). The INTS3–MISE–hSSB1 complex plays a key role in ATM activation and RAD51 recruitment to DNA damage foci during the response to genotoxic stresses. These effects on the DNA damage response are caused by the control of hSSB1 transcription via INTS3, demonstrating a new network controlling hSSB1 function.

scholarly journals ATM: Main Features, Signaling Pathways, and Its Diverse Roles in DNA Damage Response, Tumor Suppression, and Cancer Development

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 845
Author(s):  
Liem Minh Phan ◽  
Abdol-Hossein Rezaeian
Keyword(s):  
Cell Cycle ◽  
Dna Damage ◽  
Cell Cycle Arrest ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Cancer Development ◽  
Cellular Processes ◽  
Cycle Arrest ◽  
Damage Response ◽  
Cancer Cell Survival

ATM is among of the most critical initiators and coordinators of the DNA-damage response. ATM canonical and non-canonical signaling pathways involve hundreds of downstream targets that control many important cellular processes such as DNA damage repair, apoptosis, cell cycle arrest, metabolism, proliferation, oxidative sensing, among others. Of note, ATM is often considered a major tumor suppressor because of its ability to induce apoptosis and cell cycle arrest. However, in some advanced stage tumor cells, ATM signaling is increased and confers remarkable advantages for cancer cell survival, resistance to radiation and chemotherapy, biosynthesis, proliferation, and metastasis. This review focuses on addressing major characteristics, signaling pathways and especially the diverse roles of ATM in cellular homeostasis and cancer development.

scholarly journals Bisphenol A exposure triggers apoptosis via three signaling pathways in Caenorhabditis elegans

RSC Advances ◽  
2017 ◽  
Vol 7 (52) ◽  
pp. 32624-32631 ◽  
Author(s):  
Yun Wang ◽  
Lianfeng Zhang ◽  
Xun Luo ◽  
Shunchang Wang ◽  
Yuanyuan Wang
Keyword(s):  
Dna Damage ◽  
Caenorhabditis Elegans ◽  
Growth Factor ◽  
Bisphenol A ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades ◽  
Damage Response ◽  
Mitogen Activated Protein

Bisphenol A can trigger germline apoptosis via three signaling pathways including DNA damage response (DDR) pathway, mitogen-activated protein kinase (MAPK) cascades and insulin-like growth factor-1 (IGF-1) network in Caenorhabditis elegans.

scholarly journals Oncogenes and the DNA Damage Response: Myc and E2F1 Engage the ATM Signaling Pathway to Activate p53 and Induce Apoptosis

Cell Cycle ◽  
2006 ◽  
Vol 5 (8) ◽  
pp. 801-803 ◽  
Author(s):  
Sungki Hong ◽  
Raju V. Pusapati ◽  
John T. Powers ◽  
David G. Johnson
Keyword(s):  
Dna Damage ◽  
Signaling Pathway ◽  
Dna Damage Response ◽  
Damage Response ◽  
Atm Signaling Pathway ◽  
Atm Signaling

scholarly journals Crosstalk between signaling pathways and DNA damage response

2019 ◽  
Vol 1 (2) ◽  
pp. 81-91 ◽  
Author(s):  
Kangjunjie Wang ◽  
Long Li ◽  
Yuxue Zhang ◽  
Daming Gao
Keyword(s):  
Dna Damage ◽  
Signaling Pathways ◽  
Dna Damage Response ◽  
Damage Response
Sign in / Sign up

Export Citation Format

Share Document