Making and breaking the replisome in animal cells
Karim Labib
University of Dundee, Scotland (UK)
Eukaryotic cells make a single copy of the chromosomes in each cell cycle. In humans, defects in chromosome replication are intimately linked to the early development and evolution of cancer. Until recently, our understanding of eukaryotic DNA replication was largely dependent on studies of the budding yeast, Saccharomyces cerevisiae, for which the entire process of DNA replication can be recapitulated in vitro with purified proteins. Animal cells have orthologues of almost all of yeast proteins that are required for DNA replication, indicating a very high degree of evolutionary conservation. Nevertheless, recent work has identified important differences in how the replisome is assembled and disassembled in animal cells compared to yeast, highlighting the importance of studying these processes directly in metazoan species. Our group focuses on how animal cells regulate replisome biology in ways that differ from the predictions of the yeast model, using a combination of in vivo approaches in the nematode C. Elegans and studies of mammalian cells. We focus on metazoan-specific replisome biology that involves factors mutated in human disease, together with potential new targets for anti-cancer therapy.