Remarkably, cancer cells often initiate mitosis with residual DNA damage. This can be explained by a higher load of DNA lesions due to oncogene-induced replication stress, defective DNA repair or treatment with DNA damaging chemotherapeutics. In addition, cell-cycle checkpoints in cancer cells are often able to initiate but unable to maintain a cell-cycle arrest.
Intriguingly, cancer cells have apparently adapted to deal with mitotic DNA lesions. These alternative repair mechanisms in mitosis likely represent unique dependencies of cancer cells that could be therapeutically exploited. However, the components of these pathways and their regulation are currently largely unclear, and the dependency of cancer cells on these pathways is largely unexplored.
KWF recently funded a research project (total amount: 620k Euro), in which we will investigate how DNA repair is re-wired during mitosis, and what the therapeutic consequences are of targeting these mitotic pathways. Postdoc Rolf de Boer and PhD student Lauren de Haan will use biochemical, genetic and cell biological approaches to dissect mitotic DNA repair, in collaboration with the research group of dr. Puck Knipscheer (Hubrecht laboratory, Utrecht, the Netherlands).