Cellular DNA Damage Response to Zinc Oxide Nanoparticles Hinges on the Tumor Suppressor p53 Pathway

The tumor suppressor p53 regulates different cellular pathways involved in cell survival, DNA repair, apoptosis, and senescence. However, according to an increasing number of studies, the p53-mediated canonical DNA damage response is dispensable for tumor suppression. p53 is involved in mechanisms regulating many other cellular processes, including metabolism, autophagy, and cell migration and invasion, and these pathways might crucially contribute to its tumor suppressor function. In this review we summarize the canonical and non-canonical functions of p53 in an attempt to provide an overview of the potentially crucial aspects related to its tumor suppressor activity.

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Modeling the heterogeneity of p53 dynamics in DNA damage response

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720016500013 ◽

2016 ◽

Vol 14 (01) ◽

pp. 1650001 ◽

Cited By ~ 1

Author(s):

Wenlei Wu ◽

Weibin Sun ◽

Tingzhe Sun

Keyword(s):

Dna Damage ◽

Tumor Suppressor ◽

Dna Damage Response ◽

Linear Correlation ◽

Dna Lesions ◽

Theoretical Studies ◽

Tumor Suppressor P53 ◽

Damage Repair ◽

Threshold Mechanism ◽

Damage Response

The tumor suppressor p53 can be activated by DNA damage and exhibits undamped pulses. Recent reports have demonstrated a non-threshold mechanism for p53 dynamics. However, no related theoretical studies have been proposed. Here, we constructed a refined DNA damage repair model that incorporated both intrinsic and extrinsic DNA lesions. We proposed that the basal DNA damage may trigger significant fractions of p53 pulses. We also reproduced the heterogeneity of p53 dynamics in experiments. The number of p53 pulses showed no correlations with DNA damage. We also replicated the linear correlation between DNA damage and the probability of igniting a pulse. Our model has unraveled the heterogeneous p53 responses.

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Faculty Opinions recommendation of Activation of the cellular DNA damage response in the absence of DNA lesions.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1108695.571444 ◽

2008 ◽

Author(s):

Yosef Gruenbaum

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Dna Lesions ◽

Damage Response ◽

Cellular Dna

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Targeting Protein-Protein Interactions in the DNA Damage Response Pathways for Cancer Chemotherapy

RSC Chemical Biology ◽

10.1039/d1cb00101a ◽

2021 ◽

Author(s):

Kerry Silva McPherson ◽

Dmitry Korzhnev

Keyword(s):

Dna Damage ◽

Dna Damage Response ◽

Protein Interactions ◽

Cell Cycle Progression ◽

Protein Protein Interactions ◽

Cycle Progression ◽

Damage Recognition ◽

Damage Response ◽

Cellular Dna ◽

Dna Damage Recognition

Cellular DNA damage response (DDR) is an extensive signaling network that orchestrates DNA damage recognition, repair and avoidance, cell cycle progression and cell death. DDR alternation is a hallmark of...

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

Journal of Virology ◽

10.1128/jvi.79.13.8243-8248.2005 ◽

2005 ◽

Vol 79 (13) ◽

pp. 8243-8248 ◽

Cited By ~ 7

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.

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