DNA Repair and Immune Response

DNA damage refers to any modification in the structure of DNA that can affect a gene’s function. To prevent the accumulation of DNA lesions, cells have evolved with complex and overlapping DNA repair mechanisms involving highly specialized proteins that can detect and fix DNA injuries. The imbalance between DNA damage and repair impairs tissue homeostasis, accelerating the rate of the aging process and increasing the risk of developing several age-related diseases such as cancer. Noteworthy, age-related chronic low-grade inflammation is considered one of the strongest risk factors for cancer development, adding inflammation as another hallmark of these conditions. Thus, inferring changes in DNA damage responses (DDR) as a cause or consequence of other age-related inflammatory infirmities seems far from an overstatement. 

Furthermore, DDR-related proteins are not only restricted to DNA repair processes but participate in other cellular circuits that regulate cell function, including metabolism. Metabolic reprogramming of immune cells has been successfully targeted for potential therapies to treat inflammatory conditions. Similar to DDR, the cellular metabolism is also under tight control of a protein network that interprets several extra- and intracellular signals to define the cell fate via activation or inhibition of specific metabolic pathways. Although the relationship between genome instability and cell metabolism has emerged about 100 years ago when Warburg and Cori described that cancer cells preferentially fuel their growth via glycolysis instead of oxidative phosphorylation, the mechanisms that govern this cooperation are still poorly understood.  

The DDR opens news perspectives for understanding regulatory mechanisms controlling inflammation, and the in-depth comprehension of how the DDR cooperates with cellular metabolic reprogramming provides new opportunities to integrate basic science and translational research. 

This Research Topic welcomes the contribution of Original Research, Review, Mini-review, Hypothesis and Theory, and Perspective articles on DDR in the context of inflammatory and metabolic diseases (e.g., aging, cancer, atherosclerosis, and obesity), immune and non-immune cell development, and function, immunotherapy against cancer, and cell signaling and metabolism.