Projet : DNA replication origins and the 3D Genome

A recent intriguing observation of our group was a specific organization of DNA replication origins along the Topologically Associated domains (Akerman et al, 2020). Both human and mouse replication origins were significantly enriched at TAD borders, giving rise to a “smiley” line.
Therefore, the DNA replication origins density pattern mimics the structural organization of the genome in individual chromatin domains. Moreover, this distribution was disturbed during the immortalization of human breast cells. Untransformed cell types did not display such altered origin density at TAD borders, suggesting that this property is specific to cancer cell formation. This altered distribution of origins is mainly due to an increase in stochastic origins. The finding that replication origins are enriched at TAD borders might reflect a role for DNA replication origins in forming chromatin loops or their consequence. As such, the density of origins could play a role in the insulation of replication domains.
We now wish to understand how this organization allows efficient and controlled DNA replication in human cells.