Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage
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. P...
| Main Authors: | , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
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Public Library of Science
2010
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| Online Access: | http://hdl.handle.net/1721.1/55379 https://orcid.org/0000-0001-9307-6116 |
| _version_ | 1826199578931625984 |
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| author | Guerra, Lina Albihn, Ami Tronnersjö, Susanna Yan, Qinzi Guidi, Riccardo Stenerlöw, Bo Sterzenbach, Torsten Josenhans, Christine Fox, James G. Schauer, David B. Thelestam, Monica Larsson, Lars-Gunnar Henriksson, Marie Frisan, Teresa |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Guerra, Lina Albihn, Ami Tronnersjö, Susanna Yan, Qinzi Guidi, Riccardo Stenerlöw, Bo Sterzenbach, Torsten Josenhans, Christine Fox, James G. Schauer, David B. Thelestam, Monica Larsson, Lars-Gunnar Henriksson, Marie Frisan, Teresa |
| author_sort | Guerra, Lina |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T11:22:28Z |
| format | Article |
| id | mit-1721.1/55379 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T11:22:28Z |
| publishDate | 2010 |
| publisher | Public Library of Science |
| record_format | dspace |
| spelling | mit-1721.1/553792022-09-27T19:05:48Z Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage Guerra, Lina Albihn, Ami Tronnersjö, Susanna Yan, Qinzi Guidi, Riccardo Stenerlöw, Bo Sterzenbach, Torsten Josenhans, Christine Fox, James G. Schauer, David B. Thelestam, Monica Larsson, Lars-Gunnar Henriksson, Marie Frisan, Teresa Massachusetts Institute of Technology. Department of Biological Engineering Fox, James G. Schauer, David B. Fox, James G. 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. Swedish Cancer Society Swedish Research Council 2010-06-03T16:05:39Z 2010-06-03T16:05:39Z 2010-01 2009-11 Article http://purl.org/eprint/type/JournalArticle 1932-6203 http://hdl.handle.net/1721.1/55379 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. https://orcid.org/0000-0001-9307-6116 en_US http://dx.doi.org/10.1371/journal.pone.0008924 PLoS ONE Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Public Library of Science PLoS |
| spellingShingle | Guerra, Lina Albihn, Ami Tronnersjö, Susanna Yan, Qinzi Guidi, Riccardo Stenerlöw, Bo Sterzenbach, Torsten Josenhans, Christine Fox, James G. Schauer, David B. Thelestam, Monica Larsson, Lars-Gunnar Henriksson, Marie Frisan, Teresa Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title | Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title_full | Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title_fullStr | Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title_full_unstemmed | Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title_short | Myc Is Required for Activation of the ATM-Dependent Checkpoints in Response to DNA Damage |
| title_sort | myc is required for activation of the atm dependent checkpoints in response to dna damage |
| url | http://hdl.handle.net/1721.1/55379 https://orcid.org/0000-0001-9307-6116 |
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