[
International Worm Meeting,
2021]
The repair of DNA damage is crucial to ensure organismal health. However, the response to DNA damage differs depending on whether the cells are somatic or germ cells, as well as their proliferative and differentiation status. In germ cells, DNA repair is highly efficient and accurate, leading to very low mutation rates compared to somatic cells. In addition, replicating cells can use high-fidelity repair mechanisms such as homologous recombination as well as Single Strand Annealing, Microhomology End-Joining and long-patch Base Excision Repair. To repair UV-lesions, dividing cells rely on global genome nucleotide excision repair, whereas quiescent cells mostly use transcription-coupled nucleotide excision repair. In C. elegans, repair pathways are highly conserved and can be easily studied in the context of postmitotic somatic cells and the highly proliferative germline. The DRM/DREAM complex is a highly conserved transcriptional repressor of cell cycle genes that promotes quiescence. Using C. elegans, we have found that DRM can bind and repress multiple genes involved in the DNA damage response. A deficiency in the DRM complex leads to a gene expression signature with a significant component of DNA repair genes upregulated in the soma that resembles a germline-like expression pattern. DRM complex deficient mutants show a remarkable resistance to and improved repair of various DNA-damage types, both during development and aging. We propose that the DRM complex represses all major DNA repair pathways in somatic tissues, thus limiting their resistance to genotoxic stress. The DRM mutants' resistance to various DNA damage types indicates that this complex functions as a master regulator of somatic DNA repair capacity.