Final Report Summary - DDRNA (A novel direct role of non coding RNA in DNA damage response activation) Genome integrity is under constant threat. The so-called DNA damage response (DDR) is a complex machinery that deals with DNA damage generation. So far such machinery was thought to be composed uniquely by protein-protein interactions governed by post-translational modifications. With the support of ERC, we discovered that non coding RNA generated at sites of DNA damage are essential to mount a full DDR. We discovered that long RNA molecules are synthesized by RNA polymerase II from DNA ends and processed into shorter RNAs. Such RNAs are necessary for DDR activation and interact specifically with DDR proteins and among themselves. Such interactions are essential to allow DDR activation and can be manipulated by antisense tools, thus providing for the first time an unprecedented degree of specificity. This approach is effective in cultured cells and in vivo.
