New Branches in the Ever-Growing DNA Damage Response

Maintenance of genome stability is critical for cellular homeostasis and the organism’s health. The primary threat on to genome stability is DNA damage stemming from both endogenous and exogenous agents. DNA lesions activate the DNA damage response (DDR) - a complex signaling network consisting of DNA repair pathways and many other branches that profoundly modulate numerous cellular circuits. The DDR is vigorously activated by critical DNA lesions such as double strand breaks (DSBs). The breadth of this network is based on a core of DDR-dedicated proteins and temporary recruitment of hundreds of proteins from various cellular circuitries. Its complexity is evident not only from the number of its pathways and players, but also from the amount of post-translational modifications (PTMs) induced on DDR players. Yet, the DDR is extremely fine-tuned and its numerous branches are subject to strict checks and balances. We have been investigating several novel DDR players recruited by the DDR from various physiological arenas in response to DSB induction. Some of them come from the RNA processing circuits and others represent new ubiquitin-driven processes in the DDR. Examples will be presented.