DNA damage and repair mechanisms are crucial for maintaining genomic stability, and their dysregulation is closely linked to the complex pathogenesis of autoimmune diseases. The present review systematically describes the types of DNA damage, key repair pathways, their regulatory networks, and the multidimensional interactions between DNA repair and the immune system. Furthermore, it delves into how defective DNA repair drives the development of autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis through mechanisms encompassing cyclic GMP‑AMP synthase (cGAS)‑stimulator of interferon genes (STING) pathway activation, self‑antigen release and breakdown of immune tolerance. Oxidative stress‑induced DNA damage, mutations in repair genes and aberrant accumulation of cytosolic DNA are key triggers of autoimmune responses. In addition, DNA repair proteins indirectly influence disease progression by modulating immune cell functions, including T‑cell homeostasis and macrophage polarization. The present review further summarizes the therapeutic potential and challenges of targeting DNA damage response pathways, including via poly adenosine diphosphate ribose polymerase inhibitors and cGAS‑STING axis regulation, as demonstrated in pre‑clinical models. Future research leveraging multi‑omics and innovative delivery systems will be crucial for translating these discoveries into effective, personalized therapies. The present review advances the development of personalized precision medicine and provides a solid theoretical foundation for developing novel treatment strategies.
Wan et al. (Wed,) studied this question.
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