Prof. Matthias Altmeyer, University of Zurich

Cell cycle regulation and the cellular responses to replication stress and DNA damage are closely intertwined. On the one hand, the cellular mechanisms that deal with DNA lesions and their repair must integrate cell cycle information to trigger an appropriate response. On the other hand, they control cell cycle progression through cell cycle checkpoint signaling. Although pausing the cell cycle is crucial to prevent excessive amounts of DNA damage from being passed on, accumulating evidence indicates that certain replication and repair intermediates are transmitted to and processed in subsequent cell cycle phases. Moreover, repaired DNA lesions may lead to persistent epigenetic scars that affect transcription, replication, and repair programs in subsequent cell generations. We are pursuing multidimensional cell imaging approaches to investigate this intimate interplay and its implications for genome stability. In addition to providing insights into the inheritance of DNA damage and the emergence of sister cell heterogeneity, these analyses have revealed post-mitotic DNA synthesis (post-MiDAS) in G1 cells as a mechanism that resolves heritable, replication stress-associated DNA lesions after cell division. The seminar will summarize and discuss recent work that leverages complementary cell-cycle-resolved microscopy and quantitative proteomics to identify genomic regions prone to post-MiDAS and elucidate the cellular processes and protein factors that regulate this poorly characterized mechanism of genome maintenance.