DNA replication and repair machinery

The DNA replication and repair machinery is a vast collective of enzymes and proteins that ensure the high-fidelity duplication of the genome and the correction of various forms of DNA damage [1]. This system includes DNA polymerases for synthesis, helicases for unwinding the double helix, and specialized repair proteins involved in pathways such as base excision repair (BER), nucleotide excision repair (NER), and homologous recombination (HR) [2]. In oncology, this machinery is a primary target; many traditional chemotherapies work by inducing DNA lesions (e.g., platinum agents) or inhibiting replication enzymes (e.g., antimetabolites) to overwhelm the cell's repair capacity [3]. Modern targeted therapies, such as PARP inhibitors, exploit specific defects in these repair pathways through the principle of synthetic lethality, particularly in tumors with BRCA1/2 mutations [4]. Beyond cancer, deficiencies in these processes are linked to hereditary syndromes, accelerated aging, and neurodegeneration [5]. Consequently, the machinery serves as both a critical safeguard of life and a significant therapeutic vulnerability in disease states.

Other names

DNA damage response (DDR) systemGenome maintenance machineryDNA metabolic process

Inhibition of DNA polymerases, induction of DNA cross-links, inhibition of poly(ADP-ribose) polymerase (PARP), and inhibition of topoisomerases I and II.