Structure and mechanism of replication coupled histone assembly
Description: Essential biological processes such as gene expression, DNA repair and replication require dynamic assembly and disassembly of nucleosomes. These processes involve several histone chaperones that handle and escort histones. The CAF-1 complex (Chromatin Assembly Factor 1) is the only histone chaperone characterized so far to promote coupling of histones H3-H4 assembly with DNA replication. CAF-1 and its mediated nucleosome assembly pathway has recently been identified as a critical factor regulating the stability of cell identity and differentiation potential in various cell types. The action of CAF-1 is coordinated with other histone chaperones, ASF1 and the recently identified histone chaperone, associated with the replicative helicase MCM2. The key molecular determinants involved remain poorly understood. The goal of REPLICAF is to unravel the molecular mechanism underlying replication-coupled nucleosome assembly by CAF-1, ASF1, and MCM2 using structural approaches validated by functional assays. We expect to obtain fundamental insights into how epigenetic information is maintained and transmitted to the progeny during cell division with implications on cell plasticity.
Funder: Agence Nationale de la Recherche
Amount: €589,500
Funding type: research
Funder scheme: AAPG2016
Start date: 2016-10-01
Investigator: Geneviève ALMOUZNI
Institution: INSTITUT CURIE - SECT DE RECHERCHE
Funded outputs count: 25
Funder award ID: ANR-16-CE11-0028
OpenAlex ID: G1827113121