Specific ATM-Mediated Phosphorylation Dependent on Radiation Quality
| Autor: | Hengameh Zahed-Kargaran, Mary K. Whalen, Sukhleen K. Gurai, Janice M. Pluth |
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| Rok vydání: | 2008 |
| Předmět: |
Radiation quality
Kinetics Biophysics Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Protein Serine-Threonine Kinases Biology Radiation Dosage Cell Line Flow cytometry medicine Humans Radiology Nuclear Medicine and imaging Irradiation Phosphorylation Radiation medicine.diagnostic_test Tumor Suppressor Proteins Dose-Response Relationship Radiation DNA Fibroblasts Phosphoproteins DNA-Binding Proteins Biochemistry Signal transduction DNA Damage |
| Zdroj: | Radiation Research. 170:353-364 |
| ISSN: | 1938-5404 0033-7587 |
| Popis: | To determine whether the physical differences between high- and low-LET radiation are reflected in the biological responses of exposed cells, we detailed phospho-protein profiles of three proteins functional in radiation repair and signal transduction. Detailing gamma-H2AX, pATF2 Ser490/498 and pSMC1 Ser957 kinetics after X-ray and iron-ion exposure also provides a window into understanding the underlying cellular responses. Phosphorylated forms of these proteins have been documented to co-localize at sites of double-strand breaks (DSBs) after low-LET radiation exposures, and two of these phosphorylations, pATF2 and pSMC1, are specifically dependent on ATM. Flow cytometry-based methods were used to quantify total levels of each phospho-protein at various times after irradiation. As expected, we observed a greater induction and persistence in gamma-H2AX after iron-ion (high-LET) exposure compared to X-ray (low-LET) exposure. In contrast, pATF2 and pSMC1 showed markedly lower induction levels after iron-ion exposure compared to equivalent doses of X rays. Quantification of pATF2 and pSMC1 foci revealed fewer cells containing foci and fewer foci per cell after iron-ion compared to X-ray exposure. These findings suggest that ATM responds to DSBs induced by high-LET radiation differently from DSBs induced by low-LET radiation. |
| Databáze: | OpenAIRE |
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