DNA repair and genome integrity

The DNA damage response (DDR) is a complex network of pathways involving hundreds of proteins with the main goal to detect and fix lesions occurring to DNA structure, thus preserving genome stability throughout generations. To enhance repair efficiency and eventually clear unrepaired harmful cells, the DDR has under its own control the progression of cell cycle, the induction of cellular senescence and the apoptotic programme. Furthermore, cells take advantage of DDR to manage break-like structures, such as telomeres, and to check processes involving DNA ‘cut and paste’ steps like meiosis and immune response. Since all these aspects of a cell life are frequently altered in cancer, not unexpectedly, deregulation of DDR is an essential step during carcinogenesis. Indeed, even if mutations in DDR genes partially reduce the repair ability of a precancerous cell, they also enhance the possibility of oncogene mutation, allow hyper-replication and promote cell survival and adaptation in stressed conditions. On the other side, impairment of DNA repair sensitizes cancer cells to radio and chemotherapeutic agents inducing DNA damage and DDR components are promising targets to enhance therapy efficiency.