The cellular response to DNA damage factors is highly dependent on the cell cycle. We have previously discovered that during mitosis -the final step of the cell cycle – the response to DNA damage is rigorously re-wired. The current project aims to elucidate how the cellular response to DNA damage is organized throughout the cell cycle. In particular, we aim to uncover the mechanisms that determine the mitotic DNA damage response, and how these factors determine the response to chemotherapeutics and radiotherapy.
The PhD student will investigate the response to DNA damage using a combination of proteomic screens, genome engineering, (live cell) microscopy, cell biology and whole genome analysis. Initial proteomics screens will be performed with synthetic DNA constructs that resemble specific types of DNA damage with cellular extracts. Newly identified factors, along with recently discovered factors will be validated in human cell line models, equipped with CRISPR-based inducible DNA lesions. Underlying mechanisms of cell cycle-dependent DNA repair will be addressed using cell biological techniques, including live cell imaging. The PhD position will be for 4 years, and should result in a PhD thesis at the University of Groningen. The PhD student will work on this project in collaboration with a post-doc, who will also be appointed on this project.