Regulation of DNA damage and immune response pathways by post-translational protein modification

Abstract

Our cells are continuously challenged by numerous external as well as internal hazards that, if not dealt with in an appropriate manner, may interfere with critical processes and underlie disease. Therefore, they heavily rely on protective mechanisms that recognize and counteract potential risks. For example, the immune system provides a first line of defense against pathogens, which upon host invasion could cause serious illness. In addition, the well-coordinated networks of the DNA damage response detect and remove damaged nucleotides that could drive mutagenesis and thereby provoke inherited disorders, cancer or ageing-related diseases. The correct activation, execution and completion of the implicated pathways, as wel as their crosstalk, is of key importance and necessitates the well-timed and -positioned presence of proteins with the desired functionality. To a great extent, this is established by post-translational modifications (PTMs) that fine-tune protein functionality. We used a combination of biological, biochemical and microscopic approaches to determine the contribution of several PTMs to the regulation of the mechanisms that safeguard our cells.