CHK1 IN STEM CELLS · The role of Chk1 in hair follicle stem cells and skin tumorigenesis

We have found that the ablation of Chk1, a serine-threonine kinase that is activated after DNA damage, strongly reduced the formation of chemically (DMBA/TPA) induced skin tumours, thus suggesting a role of this protein in hair follicle stem cells population, from which tumours are thought to arise. We have observed that deletion of Chk1 causes cell proliferation, DNA damage, and apoptosis within the hair follicle, however the populations affected and the order of events in individual cells have not been clearly defined. I hypothesise that Chk1 deletion causes stem cells to enter an aberrant cell cycle which creates DNA damage during replication and consequently leads to cell death. The purpose of this project is to investigate how Chk1 deletion affects the quiescence, proliferation, and survival of hair follicle stem cells, and to use an in vivo chemical genetic approach to determine whether these processes can be manipulated pharmacologically.