Genetic information is encoded by the approximately 3 billion base pairs of our DNA. It is protected in a complex structure called chromatin, which includes multiple scales of organization. The basic unit of chromatin is made up of proteins called histones, around which 146 base pairs of DNA wrap. Chromatin not only protects DNA from environmental damage and stress, but also plays a crucial role in regulating DNA duplication during cell division and in regulating gene expression. It carries epigenetic marks, which can be added or removed and which control the expression of many genes, including those involved in the development of cancers.
Histone chaperones are proteins conserved in all eukaryotic organisms that facilitate the assembly and disassembly of histones on DNA to form chromatin. They are essential for maintaining epigenetic marks in the right place at the right time to maintain cell identity and avoid tumorigenesis. The histone chaperone CAF-1 (Chromatin assembly factor 1) was identified more than 35 years ago for its ability to act in concert with DNA synthesis (during cell division or DNA repair). DNA), but its mode of action has long remained very mysterious. Through a structure-function study centered on the yeast Schizosaccharomyces Pombe which offers us a simplified model of this very complex process, the “Molecular Assemblies and Genome Integrity” team in collaboration with two teams from the Curie Institute and the Synchrotron Soleil has highlighted the spatial organization of CAF-1, with both flexible regions and rigid modules, and how this ensures fine dynamics of multiple interactions of CAF-1 with its partners to promote deposition of histones coupled to DNA synthesis. This organization thus helps to guarantee the correct replication of DNA, the stability of the genome as well as the maintenance of non-expressed regions of the genome during cell divisions.
Contact at Frédéric-Joliot Institute for Life Sciences:
[1] Team « Assemblages moléculaires et intégrité du génome »
[2] Teams « Dynamique de la chromatine » at UMR3664 and « Recombinaison de l'ADN, réplication et stabilité du génome » at UMR3348