The cell cycle gene repressor DRM- complex modulates DNA damage response in Caenorhabditis elegans

Cancer is a frequent cause of death. Disturbed or inefficient DNA damage response including DNA repair, cell cycle control and apoptosis, can cause tumorigenesis. The central question for this thesis was to study the relation between DNA repair and cell cycle control. The DPL-1- RB- MuvB (DRM)- complex is a well-characterized gene repressor in the nematode Caenorhabditis elegans. Its main task is the regulation of the cell cycle by repression of different genes. Homologous complexes also exist in humans and Drosophila melanogaster. For this reason, the DRM- complex was investigated in Caenorhabditis elegans. DNA damage was applied to mutants for this complex to study the impact on larval development. Furthermore, these mutant worms were intercrossed with several mutants for DNA repair pathways to investigate the interplay of cell cycle regulation and DNA repair. Using multiple in-vivo approaches by applying different types of DNA damage to these worms and in-vitro studies with qPCR and western blot analyses provided evidence that DRM- complex mutant worms exhibit an improved response to DNA damage. This is not a consequence of accelerated cell cycle. Mutants with defects in different DNA repair pathways exhibit an arrest in larval development. Interestingly, this could be bypassed partially by intercross with mutants of the DRM- complex. In summary these data indicate that mutants defective for components of DRM- complex exhibit improved response to different DNA damaging agents and that multiple repair mechanisms are involved in this altered developmental response of DRM- complex mutants.