OMR2 Study of DNA replication program of the human genome by high-throughput single-molecule Optical Replication Mapping

At each cell division, tens of thousands of replication origins need to be activated to ensure complete genome duplication. Its deregulation can challenge genome stability and lead to cancers and other diseases. The inefficient and heterogeneous nature of mammalian origin firing has made studying replication initiation in human cells difficult. A potential solution to the problem is single molecule/cell analysis. However, although great progress has already been made in developing new genome-wide approaches to study the DNA replication program during the last decade, study of individual replication forks and origin firing is still challenging. This project aims to develop an original approach to study DNA replication forks and map replication origins genome-wide at single-molecule level. Study of replication dynamics of human cells under normal growth and upon stress, will allow us to get new important insights in DNA replication regulation, and how its deregulation lead to genome instability, and its role in human diseases.