DNA synthesis and integrity

DNA synthesis and integrity refer to the complex biological processes required for the accurate duplication of the genome and the repair of DNA damage to maintain genomic stability (NHGRI, 2023; Nature Reviews Molecular Cell Biology, 2001). This is not a single molecular target but a functional category encompassing various enzymes, such as DNA polymerases and topoisomerases, and the DNA molecule itself. In clinical oncology, these processes are targeted to induce cell death in rapidly proliferating cancer cells through mechanisms such as DNA cross-linking, antimetabolite-induced nucleotide depletion, and inhibition of repair enzymes like PARP (StatPearls, 2023; NIH, 2022). While these therapies are effective against many cancers, they often lack specificity for malignant cells, leading to significant toxicities in healthy, rapidly dividing tissues such as the bone marrow and intestinal epithelium (StatPearls, 2023). Understanding the specific defects in DNA integrity pathways, such as BRCA mutations, has led to the development of targeted therapies that exploit synthetic lethality (Nature, 2005). Additionally, inhibitors of DNA synthesis are utilized in treating viral and bacterial infections by targeting pathogen-specific replication machinery (PubChem, 2024).

Other names

DNA replicationDNA repairGenome maintenanceDNA metabolismGenomic stability

Drugs targeting this process act by inhibiting nucleotide precursor synthesis (antimetabolites), inducing DNA strand breaks or cross-links (alkylating agents and platinum compounds), or inhibiting enzymes like topoisomerases and PARP that are essential for replication and repair (StatPearls, 2023; PubChem, 2024).