Markus Christmann: Impact of epigenetic silencing and p21 on Benzo[a]pyrene-induced senescence and DNA repair repression (Project 5, 2019-2022)
This project addresses the mechanisms by which the environmental carcinogen Benzo[a]pyrene abrogates E2F1 signalling and causes the silencing of DNA repair genes as well as the induction and maintenance of cellular senescence. We will identify affected genes by genome-wide analysis of epigenetic chromatin marks, characterise the interactome of the cell cycle-dependent kinase inhibitor p21 and examine the transcriptome of cells that have evaded senescence. In this manner, we expect to gain insight into how inappropriate repair, induced by the repression of important DNA repair mechanisms, may result in an escape from senescence, thus promoting the carcinogenic effects of genotoxic agents.