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Myc is required for activation of the ATM-dependent checkpoints in response to DNA damage
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2010 (English)In: PLoS ONE, ISSN 1932-6203, Vol. 5, no 1, e8924- p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2010. Vol. 5, no 1, e8924- p.
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-130762DOI: 10.1371/journal.pone.0008924ISI: 000274114800025PubMedID: 20111719OAI: oai:DiVA.org:uu-130762DiVA: diva2:351043
Available from: 2010-09-12 Created: 2010-09-12 Last updated: 2011-02-28Bibliographically approved

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