DNA damage response (DDR) enzymes (DDR enzymes)

The DNA damage response (DDR) enzymes are a diverse group of proteins, including kinases (ATM, ATR, DNA-PK), polymerases (PARP, POLQ), and nucleases, that collectively monitor and repair DNA damage to maintain genomic integrity. These enzymes are critical for detecting various types of DNA lesions, such as single-strand and double-strand breaks, and orchestrating repair through pathways like homologous recombination (HR) and non-homologous end joining (NHEJ). In oncology, the DDR pathway is a major therapeutic target because many tumors have pre-existing defects in one repair pathway, making them uniquely dependent on alternative DDR enzymes for survival. By inhibiting these compensatory enzymes—a strategy known as synthetic lethality—drugs like PARP inhibitors can selectively induce cell death in cancer cells while sparing normal tissue. Beyond cancer, the modulation of DDR enzymatic activity is being explored for its potential in treating neurodegenerative diseases and aging-related conditions where DNA damage accumulation plays a central role.

Other names

DNA repair enzymesDNA damage response proteinsDDR pathway componentsDNA repair machinery

Inhibition of enzymatic activity (e.g., kinase or polymerase activity) to prevent the repair of DNA lesions, leading to the accumulation of DNA damage and cell death, often through synthetic lethality in repair-deficient cells.