DROSHA is recruited to DNA damage sites by the MRN complex to promote non-homologous end joining

ABSTRACT The DNA damage response (DDR) is the signaling cascade that recognizes double-strand breaks (DSBs) and promotes their resolution via repair pathways of non-homologous end joining (NHEJ) or homologous recombination (HR). We others have shown DDR activation requires DROSHA; however, whether DROSHA exerts its functions by associating with sites, what controls recruitment, how influences remains poorly understood. Here, we show associates DSBs independently transcription. Neither H2AX, nor ATM DNA-PK kinase activities are required for recruitment to break sites. Rather, interacts RAD50, inhibition MRN complex mirin treatment abolishes this interaction. inactivation RAD50 knockdown prevents and, as a consequence, also 53BP1 (also known TP53BP1) recruitment. During repair, reduces NHEJ boosts HR frequency. Indeed, increases association downstream factors such RAD51 ends. Overall, our results demonstrate recruited at directs towards NHEJ.