Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage
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Guerra-2010-Myc Is Required for.pdf
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1.95 MB
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Author(s)
Guerra, Lina
Albihn, Ami
Tronnersjö, Susanna
Yan, Qinzi
Guidi, Riccardo
Stenerlöw, Bo
Sterzenbach, Torsten
Josenhans, Christine
Fox, James G.
Schauer, David B.
Date Issued
January 2010
Journal
PLoS ONE
Publisher
Public Library of Science
Citation
Guerra, Lina et al. “Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage.” PLoS ONE 5.1 (2010): e8924. ©2010 Guerra et al.
Version
Final published version
Abstract
Background: The MYC protein controls cellular functions such as differentiation, proliferation, and apoptosis. In response to genotoxic agents, cells overexpressing MYC undergo apoptosis. However, the MYC-regulated effectors acting upstream of the mitochondrial apoptotic pathway are still unknown. Principal Findings: In this study, we demonstrate that expression of Myc is required to activate the Ataxia telangiectasia mutated (ATM)-dependent DNA damage checkpoint responses in rat cell lines exposed to ionizing radiation (IR) or the bacterial cytolethal distending toxin (CDT). Phosphorylation of the ATM kinase and its downstream effectors, such as histone H2AX, were impaired in the myc null cell line HO15.19, compared to the myc positive TGR-1 and HOmyc3 cells. Nuclear foci formation of the Nijmegen Breakage Syndrome (Nbs) 1 protein, essential for efficient ATM activation, was also reduced in absence of myc. Knock down of the endogenous levels of MYC by siRNA in the human cell line HCT116 resulted in decreased ATM and CHK2 phosphorylation in response to irradiation. Conversely, cell death induced by UV irradiation, known to activate the ATR-dependent checkpoint, was similar in all the cell lines, independently of the myc status. Conclusion: These data demonstrate that MYC contributes to the activation of the ATM-dependent checkpoint responses, leading to cell death in response to specific genotoxic stimuli.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
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DOI of Published Version
http://dx.doi.org/10.1371/journal.pone.0008924
