Nitric oxide induces ATM-dependent {gamma}H2AX formation in pancreatic {beta}-cells [Molecular Bases of Disease]

March 7th, 2014 by Oleson, B. J., Broniowska, K., Schreiber, K. H., Tarakanova, V. L., Corbett, J. A..

In this study, the effects of cytokines on the activation of DNA double-strand break repair factors H2AX and ATM were examined in pancreatic β-cells. We show that cytokines stimulate H2AX phosphorylation (γH2AX formation) in rat islets and insulinoma cells in a nitric oxide- and ATM-dependent manner. In contrast to the well-documented role of ATM in DNA repair, ATM does not appear to participate in the repair of nitric oxide-induced DNA damage. Instead, nitric oxide-induced γH2AX formation correlates temporally with the onset of irreversible DNA damage and the induction of apoptosis. Furthermore, inhibition of ATM attenuates cytokine-induced caspase activation. These findings show that the formation of DNA double-strand breaks correlates with ATM activation, irreversible DNA damage and ATM-dependent induction of apoptosis in cytokine-treated β-cells.