Modifying chromatin architecture during the response to DNA breakage

The human genome is compacted in a dynamic macromolecular complex, chromatin, whose structure presents a considerable barrier to the cellular machinery which responds to DNA double-strand breaks. This review discusses current understanding of the processes that modify chromatin architecture to enable, first, the sensing of DNA breakage, next, the assembly of the protein complexes that resolve the lesion, and finally, the restoration of epigenetic marks after its repair. The importance of these fundamental biological processes is underscored by the growing appreciation that they are aberrant in human diseases, and that their modulation could provide new approaches to disease therapy.