DNA damage repair proteins (DDR proteins)

DNA damage repair (DDR) proteins are a diverse group of enzymes and signaling factors that maintain genomic integrity by identifying and correcting DNA lesions [1, 8]. These proteins are organized into several distinct pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), homologous recombination (HR), and non-homologous end joining (NHEJ) [16, 18]. In many cancers, specific DDR pathways are defective, leading to genomic instability and a reliance on alternative repair mechanisms [6, 8]. This biological vulnerability is exploited by DDR inhibitors, such as PARP inhibitors, which induce "synthetic lethality" by blocking a backup repair pathway in cells already deficient in another [3, 10]. Beyond oncology, defects in DDR proteins are linked to neurodegenerative diseases, immunodeficiencies, and premature aging syndromes [15, 21]. Therapeutic development in this field focuses on both monotherapies for specific genetic backgrounds and combination treatments to sensitize tumors to DNA-damaging agents like chemotherapy and radiation [1, 17].

Other names

DNA repair machineryDNA damage response proteinsDDR factorsDNA repair enzymes

Inhibition of specific DNA repair enzymes to induce synthetic lethality, trap repair proteins on DNA, or sensitize cells to DNA-damaging agents.