Final Report Summary - EPIN (Maintenance of epigenome integrity in response to DNA damage)
DNA damage challenges not only genome stability but also the integrity of its organization with histone proteins into chromatin, which is central to genome functions and cell identity. This research project aimed at dissecting the fundamental mechanisms that contribute to maintaining chromatin integrity in response to DNA damage in mammalian cells. We did tackle this question at different levels of chromatin organization, from histone variant dynamics up to higher-order chromatin domains. We developed an innovative approach for real-time tracking of H3 and H4 histones after local UVC damage and determined the contribution of parental and newly synthesized histones to the maintenance of chromatin structure and function during repair progression. We also extended our analyses to follow the dynamics of H2A variants at UVC damage sites, and thus uncovered a reshaping of histone variant patterns at sites of UVC damage repair. Finally, we established a unique cellular model in mouse fibroblasts to address how higher-order chromatin organization into heterochromatin domains is preserved following UVC damage. Altogether, these complementary approaches shed new light on how genome and chromatin integrity are maintained in a coordinated manner following genotoxic stress.