Constance Alabert

DNA replication in the context of chromatin – Implications for human diseases

During lineage propagation, cells must duplicate their genetic and epigenetic information to maintain cell identity. However, the mechanisms underlying the maintenance of epigenetic information in dividing cells remain largely unknown. In S phase, progression of DNA replication forks provokes a genome-wide disruption of the epigenetic information. While nucleosomes are rapidly reassembled on newly replicated DNA, full restoration of epigenetic information is not completed until after mitosis. Our aim is to dissect the mechanisms that restore epigenetic information on newly replicated DNA. To this end we take advantage of the Nascent Chromatin Capture (NCC), a novel technology that allows the analysis of proteins associated with newly replicated DNA. We aim to identify and functionally characterize key players in the restoration of the epigenetic information in cycling cells and at specific loci. We aim to further investigate the pathological role of the newly identified chromatin factors, which are deregulated in human diseases as cancer. Altogether, these integrated approaches should provide new insights into the molecular mechanisms that coordinate genome and epigenome maintenance across cell generations.

One of the ways cells control whether genes are turned ‘on’ or ‘off’ is by placing epigenetic ‘tags’ on their DNA. But when cells are dividing, these ‘tags’ are removed, meaning they need to be put back once cells have finished dividing. Our aim is to identify and understand the mechanisms cells use to put these ‘tags’ back in the right place after cells have divided, and to find out whether they play a role in tumor development and growth.