Research in the last two decades has revealed a surprising interplay between the DNA Damage Response (DDR) and RNA biology. It has been shown that transcription and RNA processing can interfere with DNA replication, thus becoming a serious potential threat to genome stability. Reciprocally, DNA lesions able to interfere with replication and transcription globally impact on different steps of RNA metabolism including RNA splicing and stability. In addition, recent observations suggest a potential important role of non-coding RNAs in the DDR. Finally, RNAs also act as key players regulating histones modifications, chromatin and chromosome organization that further influence all DNA metabolic processes from replication to repair. Altogether this recent research puts RNA as a key molecule in the whole network of DDR with both a potential positive and negative role in genome integrity, and DDR has emerged at the center of this complex interplay between DNA synthesis, transcription, RNA processing and chromatin, with major consequences for genomic instability. The aim of this Jacques Monod conference is to bring together experts from these different rapidly-changing fields in order to discuss the most recent results on these novel and important issues. In particular, we expect to discuss the following topics: a) Transcription and RNA as threats; b) Replication conflicts; c) Nuclear compartments and the DDR; d) DSB repair; e) The RNA in the DDR; e) Chromatin modifications in genome integrity, and f) Mechanisms of telomere integrity.