The DNA-RNA hybrids are a natural occurrence within eukaryotic cells and their level are high at sites of high transcriptional activity. They are non-canonical nucleic acid structures with transcriptional regulatory functions. Their presence is reported to predispose a locus to chromosomal breakage. The S9.6 monoclonal antibody recognizes DNA-RNA hybrids (also known as R-loops) and does not bind to single or double stranded DNA. The antibody has high affinity for DNA?RNA hybrids but also binds RNA-RNA hybrids that are AU-rich. The specificity of the antibody appears to be determined by a combination of sequence and structural dependency since R?loop sequence affects binding affinity.