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DNA-PKcs and PARP1 at the interface between DNA damage responses and cGAS-STING signaling: context-dependent roles
Tiantian Miao1, Jiaqi Zhao2, Jinghong Wu2
1Department of Clinical Laboratory, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Institute, Beijing, People's Republic of China.
Aims:
To explore the roles of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and poly(ADP-ribose) polymerase 1 (PARP1) in both the DNA damage repair (DDR) pathway and the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway mediated immune response, and to analyze the therapeutic potential of their inhibitors.
Methods:
This is a review article synthesizing recent findings on the functions of DNA-PKcs and PARP1 in DDR, their context-dependent effects on the cGAS-STING pathway and the therapeutic mechanisms of their inhibitors.
Results:
DNA-PKcs and PARP1 are key components of two major DDR mechanisms. Beyond their canonical repair functions, both factors significantly regulate the cGAS-STING pathway, a central mediator linking cytoplasmic DNA and the type I interferon response.
Conclusion:
DNA-PKcs and PARP1 connect genome maintenance with innate immune signaling through context-dependent mechanisms. Targeting these proteins represents a promising strategy for modulating cGAS-STING signaling and improving disease treatment.
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