Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

SIMPLE SUMMARY: Cells respond to genotoxic stress through complex protein pathways called DNA damage response (DDR). These mechanisms ensure the preservation of genomic integrity and activate DNA repair, cell cycle regulation, and, ultimately, programmed cell death. When altered, the DDR protein network leads to several diseases, particularly cancers. In recent years, the vulnerabilities of the DDR network have been successfully exploited to improve cancer treatments using DNA damage strategies and therapies combination. ABSTRACT: Cells respond to genotoxic stress through a series of complex protein pathways called DNA damage response (DDR). These monitoring mechanisms ensure the maintenance and the transfer of a correct genome to daughter cells through a selection of DNA repair, cell cycle regulation, and programmed cell death processes. Canonical or non-canonical DDRs are highly organized and controlled to play crucial roles in genome stability and diversity. When altered or mutated, the proteins in these complex networks lead to many diseases that share common features, and to tumor formation. In recent years, technological advances have made it possible to benefit from the principles and mechanisms of DDR to target and eliminate cancer cells. These new types of treatments are adapted to the different types of tumor sensitivity and could benefit from a combination of therapies to ensure maximal efficiency.