Single-stranded DNA within R-loop (ssDNA in R-loop)

Single-stranded DNA (ssDNA) within an R-loop is the displaced DNA strand formed when an RNA transcript hybridizes with the template DNA strand, creating a three-stranded structure (Nature Reviews Genetics, 2015). While R-loops play physiological roles in processes like immunoglobulin class switching and gene expression regulation, their persistence is a major driver of genomic instability (Genes & Development, 2017). The exposed ssDNA is particularly vulnerable to chemical damage and mutagenic enzymes, leading to transcription-replication conflicts and DNA double-strand breaks (Cell, 2016). In clinical development, this structure is targeted indirectly through the inhibition of enzymes like Topoisomerase I, which prevents R-loop accumulation, or by using ATR and PARP inhibitors to exploit the DNA damage response in R-loop-heavy cancer cells (Molecular Cell, 2019). Therapeutic strategies aim to capitalize on the R-loop stress characteristic of certain tumors to induce selective cell death (Trends in Cancer, 2020). Furthermore, the ssDNA portion is a substrate for enzymes like AID/APOBEC, which can be modulated for therapeutic effect in immune-related contexts (Nature, 2008). Monitoring these structures often involves the use of the S9.6 antibody or RNase H1-based assays to assess genomic risk (Nucleic Acids Research, 2011).

Other names

Displaced DNA strandNon-template DNA strandR-loop displaced strandR-loop ssDNA

Stabilization of R-loop structures and induction of transcription-replication conflicts leading to DNA damage and synthetic lethality.