Double-stranded B-form DNA (B-DNA)

Double-stranded B-form DNA (B-DNA) is the most biologically prevalent structural conformation of the DNA double helix under physiological conditions, characterized by a right-handed spiral with approximately 10.5 base pairs per turn [1]. It features distinct major and minor grooves that serve as critical recognition and binding sites for regulatory proteins and therapeutic small molecules [2]. As the primary repository of genetic information, B-DNA is essential for cellular survival, serving as the template for both semi-conservative replication and RNA transcription [2][3]. In clinical practice, B-DNA is a major target for cytotoxic chemotherapy; agents such as cisplatin and anthracyclines disrupt its structure to trigger apoptosis in rapidly proliferating cancer cells [3][5]. Additionally, B-DNA is a central autoantigen in autoimmune pathologies like systemic lupus erythematosus, where anti-dsDNA antibodies are used as a hallmark diagnostic and prognostic biomarker [4]. However, because B-DNA is present in all nucleated cells, drugs targeting it often possess a narrow therapeutic window and carry significant risks of long-term genomic instability and secondary cancers [5]. [1] Watson JD, Crick FH. Nature. 1953;171(4356):737-738. [2] Neidle S. Principles of Nucleic Acid Structure. Academic Press; 2007. [3] Hurley LH. Nature Reviews Cancer. 2002;2(3):188-200. [4] Rekvig OP. Frontiers in Immunology. 2020;11:585. [5] Pommier Y, et al. Nature Reviews Cancer. 2010;10(8):581-596.

Other names

B-DNAWatson-Crick DNARight-handed double helixdsDNAB-form deoxyribonucleic acid

Drugs targeting B-DNA typically act through several distinct mechanisms: intercalation between base pairs to inhibit topoisomerases and polymerases (e.g., doxorubicin), covalent alkylation and interstrand/intrastrand cross-linking (e.g., cisplatin, cyclophosphamide), minor groove binding (e.g., netropsin), or the induction of oxidative DNA strand breaks (e.g., bleomycin) [3][5].