Annuaire
Chromatin Architecture in Replication and Repair (CARR)
DNA double-strand breaks (DSBs) and replication stress are major threats to genome integrity that can lead to mutations and ultimately drive cancer development or other genetic diseases. Understanding the molecular mechanisms by which cells detect and respond to these challenges is therefore essential. Such knowledge will not only provide insight into how cells preserve genome stability under stress but also improve our understanding of how clinically used drugs exert their effects, ultimately paving the way for the discovery of new therapeutic targets.
While cellular responses to DNA double-strand breaks (DSBs) and replication stress are generally well characterized, key aspects remain unclear, particularly the 3D chromatin organization around DNA lesions. Existing techniques like Hi-C and Micro-C lack the resolution needed for detailed analysis. Additionally, stress responses are multistep processes with unique dynamics, but high cell-to-cell variability complicates accurate interpretation. Traditional assays like ChIP-seq, MNase-seq, End-seq, and Hi-C provide population-averaged data that conceals cell-to-cell heterogeneity and hinders accurate interpretation.
To address these issues, we will use the Proximity Copy Paste (PCP) method, which I developed during my postdoctoral research (Delamarre et al., 2025) to decipher the role of chromatin architecture in Replication and Repair. PCP detects multi-way chromatin interactions, DNA-bound protein footprints at base-pair resolution, and nucleosome spacing on single DNA molecules, offering unprecedented insights into chromatin structure and variability at the molecular level.
Funding: ATIP-avenir
