Inverted repeat sequences are known to form cruciform structures in negatively supercoiled DNA. They are widespread in the genomes of both eukaryotes and prokaryotes, occurring more often than expected among random sequences. In some bacteria, extrusion of cruciform DNA is required for initiation of replication and transcription, though certain inverted repeat sequences are unstable when subcloned into bacteria. Because such structures might impair DNA replication fidelity, the role of inverted repeats in mutagenesis and in human diseases has been widely studied.