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Mechanisms of the DNA damage response

Mechanisms of the DNA damage response

Fundamental molecular and cellular studies

This research line addresses the fundamental mechanistic aspects of the DNA damage response, with special attention to DNA repair by homologous recombination. We take complementary and interwoven approaches at both the molecular and cellular level. The molecular mechanisms of the multiple pathways of the DNA damage response are studied by applying and developing (single molecule) biochemical analyses, advanced proteomic analyses and state-of-the-art molecular imaging techniques to identify dynamic molecular interactions that are responsible for the assembly and disassembly of the molecular factories that guard and repair the genome. At the cellular level the DNA damage repair processes in (live) cells are monitored in real time for how they detect DNA damage and proceed to assemble and disassemble the repair machinery by applying the latest super-resolution techniques to understand the interplay between different DNA damage response pathways and their integration in the physiology of the cell.

The ultimate goal is be to define and dissect the molecular circuits of DNA damage repair and their integration in cellular processes. This knowledge is pivotal for identifying molecular targets for designing novel mechanism-based interventions and manipulations of these processes. This will provide the basis for improving existing approaches and developing entirely novel and innovative precision therapies for cancer and aging-related diseases.

Molecular circuits of DNA damage repair