Grant: Operating Grant

DNA replication is a biological process that occurs in all living organisms and copies their genetic information which is inherited by newly divided cells. Hence, faithful DNA replication is essential to all life. It has been known for many years that compounds that interfere with DNA replication, kill actively proliferating cancer cells. These compounds show severe cytotoxic effects on actively growing cells by inducing DNA damage such as double-strand breaks. In normal cells, DNA repair acts as a defence mechanisms against anticancer drugs, while in cancer cells, this mechanism often causes reduced sensitivity of these cells to the drugs. We aim to understand how DNA repair affects the cell ability to repair double-strand breaks by homologous recombination during DNA replication. This process act by copying DNA sequences from homologous DNA sequences. However, this process is highly regulated by positive (pro-recombination) and negative (anti-recombination) forces. When this balance is compromised, DNA repair cannot act properly, leading to genomic instability, an hallmark of cancer. Using genetic and cellular tools, we will investigate how/when/why this balance occurs specifically during DNA replication. In the future, this knowledge will help clinicians to optimize chemotherapy during DNA replication, by selectively inactivating the balance between pro-and anti-recombinases, leading to cancer cell death.