DNA damage signalling in D. melanogaster requires non-apoptotic function of initiator caspase Dronc

ϒH2Av response constitutes an important signalling event in DNA damage sensing ensuring effective repair by recruiting DNA repair machinery. In contrast, the occurrence of ϒH2Av response has also been reported in dying cells where it is shown to require activation of CAD (caspase activated DNase). Moreover, caspases are known to be required downstream of DNA damage for cell death execution. We show, for the first time, that initiator caspase Dronc, independent of executioner caspases, acts as an upstream regulator of DNA Damage Response (DDR) by facilitating ϒH2Av signalling perhaps involving non-apoptotic function. Such ϒH2Av response is mediated by ATM rather than ATR, suggesting that Dronc function is required upstream of ATM. In contrast, ϒH2Av appearance during cell death requires effector caspase and is associated with fragmented nuclei. Our study uncovers a novel function of Dronc in response to DNA damage aimed at promoting DDR via ϒH2Av signalling in intact nuclei. We propose that Dronc plays a dual role that can either initiate DDR or apoptosis depending upon the level and the required threshold of its activation in damaged cells.