DNA replication and repair pathway (DDR)

The DNA replication and repair pathway is a comprehensive network of biological processes essential for maintaining the integrity of the cellular genome. It encompasses several specialized sub-pathways, including base excision repair (BER), nucleotide excision repair (NER), mismatch repair (MMR), and homologous recombination (HR), which collectively detect and correct DNA lesions [Jackson & Bartek, 2009, Nature]. These processes are tightly regulated by the DNA damage response (DDR) signaling system, which coordinates DNA repair with cell cycle progression and apoptosis [O'Connor, 2015, Molecular Cell]. In clinical oncology, this pathway is a major therapeutic target; for example, PARP inhibitors exploit "synthetic lethality" in tumors with existing defects in homologous recombination, such as those with BRCA1/2 mutations [Lord & Ashworth, 2012, Nature]. Furthermore, many conventional chemotherapies, such as platinum-based agents, function by inducing overwhelming DNA damage that exceeds the pathway's repair capacity, leading to cancer cell death [Pearl et al., 2015, Nature Reviews Cancer].

Other names

DNA damage responseGenome maintenance pathwayDNA repair machinery

Inhibition of DNA repair enzymes (e.g., PARP), induction of DNA damage through alkylation or cross-linking, and inhibition of cell cycle checkpoint kinases (e.g., ATR, ATM, WEE1) to promote mitotic catastrophe.