Simon Holst Bekker-Jensen

In early work, Bekker-Jensen co-discovered the histone ubiquitination pathway in the DNA damage response (DDR). Using genetic screens, advanced imaging and mass spectrometry, he and his colleagues characterized the pathway by which cells detect and mark up DNA double-stranded breaks for repair. This included a full description of how the ubiquitin ligase RNF8 is recruited to ATM-phosphorylated H2AX-MDC1 to ubiquitinate histone H1, facilitating the handover to the ligase RNF168 which ubiquitinates histone H2A. These ubiquitin marks serve as a recruitment platform for a host of DDR factors of which Bekker-Jensen identified and functionally described several.

In recent work, Bekker-Jensen has studied translational stress responses and ribosome surveillance mechanisms, in particular the so-called ribotoxic stress response (RSR). This pathway depends on translation stress sensing by the MAP3K ZAKa and ensuing signaling through the p38 and JNK kinases. Besides obtaining mechanistic insight into the workings of this signaling pathway, Bekker-Jensen recently discovered a link to metabolic regulation, highlighting ribosomes as physiologically relevant platforms for metabolic stress signaling. 

In his most recent contribution to the fields of cellular stress signaling, DDR and translation control, Bekker-Jensen discovered the central role of mRNA damage, ribosomal signaling and the RSR in orchestrating cell death and inflammation in UV-irradiated skin. In human keratinocytes, this manifests as both rapid p38-dependent pyroptosis and slower JNK-dependent apoptosis.