|Krassimir Joseph Yankulov
Department of Molecular and Cellular Biology, University of Guelph, Guelph, Canada
DNA replication in eukaryotes is accompanied by the disassembly and reassembly of nucleosomes and the transmission of the existing epigenetic marks to the newly assembled chromatids. Several highly conserved histone chaperones are central to these processes. The establishment and maintenance of the epigenetic landscape of the cells is essential during the development and differentiation in metazoan while loss of epigenetic information has been associated with various human disorders including cancer.
Replication forks pause at numerous positions throughout the genome, but it is not known if and how the stalling of the forks affects the reassembly and the maintenance of chromatin. In my lab we study these processes using S. cerevisiae as a model organism. We apply drug-free gene silencing assays to analyze the genetic interactions between fork-associated histone chaperones (CAF1, ASF1, FACT) and genes that regulate the stability of the paused replisome (TOF1) and the resumption of elongation (RRM3). We also study the regulation of CAF1 by protein kinases involved in the regulation of DNA replication and the cell cycle (DDK and CDK).
In this presentation I will discuss our recent results on the genetic interactions between these factors and provide insights on how DNA replication and the reassembly of nucleosomes is coordinated. I will present a model suggesting that the pausing of the replication leads to epigenetic instability.