topoisomeraasi

Topoisomerase, sometimes referred to in Finnish as topoisomeraasi, is a class of enzymes that regulate the topological state of DNA by transiently breaking and rejoining strands. They relieve or introduce DNA supercoiling and resolve entanglements that arise during processes such as replication, transcription, recombination, and chromatin organization. Topoisomerases are divided into two main types: type I and type II. Type I enzymes cleave a single DNA strand and alter the linking number by increments of one without requiring ATP in many cases. Type II enzymes cut both DNA strands, pass another duplex through the break to change the linking number by two, and typically require ATP for activity. Type II enzymes can also decatenate intertwined circular DNA molecules.

The catalytic mechanism involves a transient covalent enzyme–DNA intermediate formed by a catalytic tyrosine that forms a phosphodiester bond with DNA. After strand passage, the break is resealed, restoring DNA integrity. This transient cleavage allows controlled topological rearrangements without permanently fragmenting the genome.

In cells, topoisomerases participate in replication fork progression, transcription, chromosome condensation and segregation, and genome maintenance. Eukaryotes express multiple isoforms, such as Topo I and Topo II (with alpha and beta variants), which have distinct cellular roles and regulatory properties.

Clinical and pharmacological relevance is notable. Bacterial topoisomerases are targeted by fluoroquinolone antibiotics. In humans, topo I inhibitors (such as camptothecin-derived drugs) and topo II inhibitors (such as etoposide and doxorubicin) are used in cancer therapy. These inhibitors stabilize the enzyme–DNA cleavage complex, leading to DNA damage and cell death.