title: Specific ATM-mediated phosphorylation dependent on radiation quality.
abstract: 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.
authors.affiliation: Lawrence Berkeley National Laboratory, Life Sciences Division, Berkeley, California 94720, USA.
authors.forename: Mary K
authors.initials: MK
authors.lastname: Whalen
authors.forename: Sukhleen K
authors.initials: SK
authors.lastname: Gurai
authors.forename: Hengameh
authors.initials: H
authors.lastname: Zahed-Kargaran
authors.forename: Janice M
authors.initials: JM
authors.lastname: Pluth