Nuclear double-stranded DNA (dsDNA)

Nuclear double-stranded DNA (dsDNA) is the fundamental molecule that stores the genetic blueprint of eukaryotic cells, organized into chromosomes within the nucleus. It serves as the essential template for DNA replication and RNA transcription, making its structural integrity vital for cellular survival and proliferation. In oncology, dsDNA is a primary therapeutic target, especially in tumors characterized by DNA damage response (DDR) defects, such as those with BRCA1/2 mutations or homologous recombination deficiency (HRD) (O'Connor, 2015, PMID: 26412304). These defects render cancer cells unable to repair specific types of DNA damage, such as double-strand breaks, which can be induced by platinum-based chemotherapeutics or alkylating agents. This vulnerability is exploited through the principle of synthetic lethality, where the combination of an endogenous repair defect and drug-induced damage leads to catastrophic genomic instability and selective apoptosis of cancer cells while ideally sparing healthy cells with intact DDR mechanisms (Lord & Ashworth, 2012, PMID: 22258511).

Other names

Genomic DNAChromosomal DNANuclear DNAnDNADeoxyribonucleic acid

Induction of structural DNA lesions, such as inter-strand and intra-strand cross-links, base alkylation, or stabilization of topoisomerase-DNA cleavage complexes, which lead to double-strand breaks and trigger apoptosis, particularly in cells with compromised repair pathways (Pommier et al., 2009, PMID: 19476376).