Many bacterial genomic DNAs and many viral DNAs are circular molecules. Circular DNA molecules also occur in mitochondria, which are present in almost all eukaryotic cells, and in chloroplasts, which are present in plants and some unicellular eukaryotes. Although eukaryotic nuclear DNA is linear, long loops of DNA are fixed in place within chromosomes (see Chapter 8). Each of the two strands in a circular DNA molecule or in a fixed loop of a eukaryotic chromosome forms a closed structure without free ends and is therefore subject to torsional stress.

Most bacterial DNA in chromosomes and DNA isolated from viruses containing circular double-stranded DNA is underwound, meaning that it has fewer helical turns than B-form linear DNA of the same length. As a result, the DNA molecule twists back on itself like a twisted rubber band, forming supercoils (Figure 5-8a). Localized unwinding or overwinding of a DNA molecule, which occurs during DNA replication and transcription, induces torsional stress into the remaining portion of the molecule because the ends of the strands are not free to rotate. All cells, however, contain topoisomerase I, which can relieve the torsional stress that develops in cellular and viral DNA molecules during replication and transcription. This enzyme binds to DNA at random sites and breaks a phosphodiester bond in one strand. Such a one-strand break in DNA is called a nick. The broken end then winds around the uncut strand, leading to loss of supercoils (Figure 5-8b). Finally, the same enzyme joins (ligates) the two ends of the broken strand. Another type of enzyme, topoisomerase II, makes breaks in both strands of a double-stranded DNA and then religates them. As a result, topoisomerase II can both relieve torsional stress and link together two circular DNA molecules as in the links of a chain.