Upon the induction of DNA damage, cells initiate a protective response, referred to as the DNA damage response (DDR), to repair DNA damage and maintain genome integrity. This response is driven... Show moreUpon the induction of DNA damage, cells initiate a protective response, referred to as the DNA damage response (DDR), to repair DNA damage and maintain genome integrity. This response is driven and regulated by posttranslational protein modifications and chromatin remodeling events. Mutations or aberrant expression of chromatin modifying proteins not only impacts on the DDR, but also causes human diseases with severe clinical phenotypes, illustrating the importance of these proteins for genome stability maintenance and human health. Largely unclear is, however, which and how chromatin modifying enzymes control the complex DDR pathways and in this manner prevent the onset of disease. To this end, we employed cross-disciplinary approaches that combined cell biological, biochemical and microscopic methods to identify histone modifying enzymes, chromatin remodelers as well as other DDR proteins and elucidate their mechanistic role in the response to DNA doublestrand breaks (DSBs) and disease prevention. Show less
