Single-stranded DNA (ssDNA)

Single-stranded DNA (ssDNA) is a critical nucleic acid intermediate formed during essential cellular processes such as DNA replication, repair, and transcription [Nature Reviews Molecular Cell Biology, 2017]. Under physiological conditions, ssDNA is transient and rapidly protected by single-stranded DNA-binding proteins (SSBs), most notably Replication Protein A (RPA), which prevents the formation of deleterious secondary structures and protects the strand from nuclease degradation [PubMed: 21760606]. In clinical pathology, the accumulation of ssDNA is a hallmark of replication stress and genomic instability, frequently observed in various cancers where it serves as a substrate for DNA damage response signaling [Cancer Research, 2019]. Furthermore, ssDNA acts as a potent autoantigen in systemic lupus erythematosus (SLE), where the presence of anti-ssDNA antibodies is a recognized diagnostic biomarker for disease activity [Arthritis & Rheumatology, 2020]. It also functions as a pathogen-associated molecular pattern (PAMP) that can trigger innate immune responses through sensors like Toll-like receptor 9 (TLR9) [Immunity, 2011]. Therapeutic strategies include the use of cytotoxic alkylating agents and platinum-based drugs that react with DNA bases, as well as emerging small-molecule inhibitors designed to disrupt ssDNA-protein interactions to induce synthetic lethality in tumor cells.

Other names

ssDNADenatured DNASingle-strand deoxyribonucleic acid

Drugs targeting ssDNA or its associated processes typically work by inducing covalent DNA cross-links, causing strand breaks, or inhibiting the protective proteins like RPA that stabilize ssDNA during replication [PubMed: 28475916]. In autoimmune contexts, therapies aim to deplete the B-cell populations that produce anti-ssDNA antibodies or block the downstream inflammatory signaling pathways [NCBI: NBK493173].