Our genome is constantly challenged by endogenous and exogenous DNA damage, causing thousands of DNA lesions per day. The integrity of our genome is ensured by multiple DNA repair pathways that protect from mutations and chromosomal translocations. During the last decade, several studies have unveiled the key contribution of chromatin dynamics and histone post-translational modifications in the response to DNA damage. Conversely, DNA damage leads to massive chromatin rearrangements which can hinder DNA transactions such as transcription or replication. In this talk, I will present some previous works describing how the pre-existing chromatin landscape shapes DSB-induced histone variant H2A.X phosphorylation, and how the ubiquitin system regulates transcription at DNA breaks. Finally, I will present recent findings from the lab that have revealed a tight cooperation between histone chaperones and histone-modifying enzymes in the maintenance of heterochromatic histone marks following UV.