Sophie POLO – Laboratory of Epigenome Integrity, Epigenetics & Cell Fate Centre, CNRS/Université de Paris, France

The response to DNA damage in the cell nucleus proceeds on a chromatin substrate, whose integrity is central to cell functions and identity. The coordinated maintenance of genome stability and of its organization into chromatin when challenged by genotoxic stress is thus critical. Yet, the underlying mechanisms are largely unknown and how much the DNA damage response impacts the chromatin landscape is poorly understood. We approach these issues by investigating alterations in histone variant patterns at sites of DNA damage in mammalian cells. By combining in vivo tracking of newly synthesized histones and localized UVC damage, we have uncovered histone deposition pathways involved in restoring chromatin structure and transcriptional activity in response to genotoxic stress.

We have also set up an innovative system for simultaneous visualization of new and parental histone dynamics at sites of DNA damage, which provided interesting insights into how the original information conveyed by chromatin may be preserved and unveiled a reshaping of histone variant patterns during chromatin repair. I will present our latest findings on these topics and discuss their implications for the maintenance of chromatin integrity following DNA damage.