Topoisomerasens

Topoisomerasens, or topoisomerases, are essential enzymes that regulate the topology of DNA. They solve problems caused by DNA winding during processes such as replication, transcription, and chromosome segregation by creating transient breaks in the DNA backbone, allowing strands to pass and then resealing. This activity relieves torsional stress and untangles knots and tangles that arise as DNA is copied and read.

There are two main classes: Type I and Type II. Type I topoisomerases induce single-strand breaks and change the DNA linking number in steps of one. Type II topoisomerases induce double-strand breaks and change the linking number in steps of two; they require ATP hydrolysis to power strand passage. Both classes use a catalytic mechanism that involves a covalent enzyme-DNA intermediate at an active-site tyrosine, through which DNA strands are temporarily passed before the breaks are repaired.

In bacteria, distinct Type IIA topoisomerases include DNA gyrase, which introduces negative supercoils, and topoisomerase IV, which helps decatenate replicated chromosomes. In eukaryotes, the principal enzymes are Topoisomerase I and Topoisomerase II, with Topo I primarily relaxing supercoils and Topo II resolving tangles and aiding chromosome segregation during cell division.

Medical relevance stems from the enzymes’ essential roles. Bacterial topoisomerases are targets of fluoroquinolone antibiotics, which inhibit bacterial DNA replication. In humans, topoisomerase inhibitors such as irinotecan and topotecan (Topo I) and etoposide or doxorubicin (Topo II) are used in cancer therapy; these agents often act as poisons that stabilize enzyme-DNA complexes, increasing DNA damage in cells.