Replication fork repair and Chromatin assembly

The maintenance of genome integrity occurs in the context of DNA packaged into chromatin. Chromatin constitutes a barrier to DNA replication and repair machineries that should be first lifted and then restored behind the replication fork or once the repair event is achieved. Genomes are routinely exposed to a variety of DNA damages that induce profound chromatin rearrangements and pose serious threat to epi-genome integrity during DNA replication.

Despite the recent identification of chromatin restoration pathways upon DNA repair, the crosstalk and coordination between both processes, that is likely key to safeguard genome integrity, remain poorly understood. Histones deposition on DNA is facilitated by a family of proteins called histone chaperones. At replication forks, several histone chaperones are at work to regulate histones flux. The Chromatin Assembly Factor 1 (CAF-1) promotes the direct deposition of H3-H4 in a manner coupled to DNA synthesis.

xThe team has revealed novel functions of CAF-1 in promoting HR-dependent events at stressed forks  by stabilizing D-loop intermediates and counteracting D-loop disassembly by the helicase Rqh1-mediated. Ours future directions are to investigate CAF-1 interaction networks to understand its function in chromatin assembly and in maintaining genome stability at DNA repair/replication stress sites, in yeast and humans.