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. A locus forming an DNA:RNA creates a double-stranded A/B intermediate conformation, with a second target for single-stranded nucleic acid binding proteins on the complementary, displaced DNA strand. They are shown to be resistant to the activity of DNA methyltransferases. The formation of DNA:RNA hybrids has been associated with a number of neurological diseases. Mutations in the DNA:RNA helicase senataxin (SETX) are implicated in the dominant juvenile form of amyotrophic lateral sclerosis type 4 and a recessive form of ataxia oculomotor apraxia type 2.