Stopping DNA Damage: A Newly Discovered Protein-Enhancing DNA Repair Mechanisms

Endogenous factors, such as reactive oxygen species, and exogenous factors, including ionizing radiation, ultraviolet light, and chemical agents frequently cause DNA damage. This damage compromises genomic stability, leading to mutations, cellular dysfunction, and diseases such as cancer and neurodegenerative disorders. To counteract these threats, cells utilize DNA repair pathways including direct reversal, base excision repair, nucleotide excision repair, mismatch repair, and double-strand break (DSB) repair. These mechanisms are essential for maintaining genomic integrity and ensuring the accurate transfer of genetic information. Deinococcus radiodurans exhibits extraordinary resistance to DNA-damaging agents through a combination of strategies, including an efficient DNA repair system and specialized DNA damage response proteins. Among these, DdrC is a unique DNA-binding protein that recognizes and stabilizes damaged DNA, preventing single-strand breaks from escalating into DSBs. Structural studies show that DdrC functions as a dimer with two distinct DNA-binding sites, enabling it to scan DNA for lesions and compact damaged regions. This compaction not only stabilizes DNA but also aids in preserving nucleoid integrity under extreme conditions. The ability of DdrC to bind and compact damaged DNA suggests potential applications in medicine and biotechnology. In cancer therapy, DdrC could disrupt repair mechanisms in tumor cells, enhancing the effects of existing treatments. Its role in stabilizing DNA makes it a candidate for mitigating age-related genomic instability and protecting neurons in neurodegenerative diseases. However, challenges remain, including its bacterial origin, the need for adaptation to human systems, and the development of precise delivery methods. This review provides an overview of DNA damage and repair mechanisms, the properties of DdrC, and its potential for advancing DNA repair-based therapies. While further research is required, DdrC represents a promising step toward innovative approaches to addressing genomic instability.