The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
A plausible model for the digital response of p53 to DNA damage
Open accessAbstract
Recent observations show that the single-cell response of p53 to ionizing radiation (IR) is “digital” in that it is the number of oscillations rather than the amplitude of p53 that shows dependence on the radiation dose. We present a model of this phenomenon. In our model, double-strand break (DSB) sites induced by IR interact with a limiting pool of DNA repair proteins, forming DSB–protein complexes at DNA damage foci. The persisting complexes are sensed by ataxia telangiectasia mutated (ATM), a protein kinase that activates p53 once it is phosphorylated by DNA damage. The ATM-sensing module switches on or off the downstream p53 oscillator, consisting of a feedback loop formed by p53 and its negative regulator, Mdm2. In agreement with experiments, our simulations show that by assuming stochasticity in the initial number of DSBs and the DNA repair process, p53 and Mdm2 exhibit a coordinated oscillatory dynamics upon IR stimulation in single cells, with a stochastic number of oscillations whose mean increases with IR dose. The damped oscillations previously observed in cell populations can be explained as the aggregate behavior of single cells.
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Cites
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Self-citationLane, D. P. (1992) · Nature · doi:10.1038/358015a0 · Cited by 5,138
DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation
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Self-citationEvidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses
Rothkamm, K., & Löbrich, M. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0830918100 · Cited by 1,645
Control of Stochasticity in Eukaryotic Gene Expression
Raser, J. M., & O'Shea, E. K. (2004) · Science · doi:10.1126/science.1098641 · Cited by 1,425
Requirement of the MRN complex for ATM activation by DNA damage
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Mono- Versus Polyubiquitination: Differential Control of p53 Fate by Mdm2
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Association of p19ARF with Mdm2 inhibits ubiquitin ligase activity of Mdm2 for tumor suppressor p53
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Accelerated MDM2 auto‐degradation induced by DNA‐damage kinases is required for p53 activation
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Suh, E.-K., Yang, A., Kettenbach, A., Bamberger, C., Michaelis, A. H., Zhu, Z., Elvin, J. A., Bronson, R. T., Crum, C. P., & McKeon, F. (2006) · Nature · doi:10.1038/nature05337 · Cited by 549
Recurrent Initiation: A Mechanism for Triggering p53 Pulses in Response to DNA Damage
Batchelor, E., Mock, C. S., Bhan, I., Loewer, A., & Lahav, G. (2008) · Molecular Cell · doi:10.1016/j.molcel.2008.03.016 · Cited by 422
Two-phase dynamics of p53 in the DNA damage response
Zhang, X.-P., Liu, F., & Wang, W. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1100600108 · Cited by 333
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Metadata
- Authors
- Ma, L., Wagner, J., Rice, J. J., Hu, W., Levine, A. J., & Stolovitzky, G. A.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2005-09-26
- Volume
- 102
- Issue
- 40
- Pages
- 14266-14271
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2085418817
- Cited by
- 356
- References
- 10
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- green
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- Ma, L., Wagner, J., Rice, J. J., Hu, W., Levine, A. J., & Stolovitzky, G. A. (2005). A plausible model for the digital response of p53 to DNA damage. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0501352102
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
