Myosin VI and its Role in the DNA Damage Response

Abstract

strand break (DSB) repair (53BP1, phospho-ATM and phospho-Histone H2A.X), vitality and cell cycling by performing high resolution 3D imaging (in fixed and live cells) using spinning disk microscopy. DSB were produced by X-ray irradiation. X-ray irradiated (6 Gy) Mia PaCa-2 cells in co-culture with unirradiated cells showed highly significantly less DSB relative to irradiated cells cultured alone. Intriguingly, the presence of unirradiated Mia PaCa-2 cells resulted in a rapid DBS repair in irradiated ATM -/fibroblasts down to levels of ATM þ/þ fibroblasts within 1 d after irradiation. Additionally, when irradiated Mia PaCa-2 cells were co-cultured with ATM -/fibroblasts or ATM þ/þ fibroblasts pretreated with an ATM inhibitor, the acceleration of DNA damage foci was completely abrogated similar to non-coculture conditions. Our findings suggest that ATM is a key transducer in cell-cell communication eliciting a rescue of neighboring cells from radiogenic DNA damage through a yet to be identified mechanism. Consequently, normal cells support each other in surviving radiogenic DNA damage, while cancer cells might be prone to develop resistances to current radiochemotherapies.