Chromosome and chromatin dynamics at DNA double Strand breaks

DNA double-strand break repair is an essential process ensuring the maintenance of genome integrity and recently, a transcription-coupled arm of DSB repair has been identified (named TC-DSBR for Transcription-Coupled DSB Repair). Using a cell line, called DIvA (for DSB Inducible via AsiSI), where multiples breaks are induced at annotated positions, combined with genome-wide, high throughput sequencing-based techniques (ChIP-seq, HiC...) we investigate the contribution of chromatin and chromosome conformation in the response to TC-DSB, induced in transcriptionally active loci. I will present our recent work, on the contribution of chromatin and Topologically Associating Domains (TADs) during DSB repair. More specifically we recently demonstrated the role of cohesin-mediated loop extrusion in establishing gammaH2AX on an entire TAD in cis to DSBs. We further provided evidence that when established, TAD stamped with gammaH2AX  further self-segregate in the nucleus, forming a novel DSB-induced chromatin compartment (the “D” compartment) that contributes to the activation of the DNA damage response. Finally, we recently identified the PER complex, a molecular device ensuring circadian oscillations, as a key component of TC-DSB Repair through a previously unsuspected role in positioning DSBs at the periphery of the nucleus.