Topoisomeras

Topoisomerases are enzymes that regulate DNA topology by creating transient breaks in the DNA backbone to relieve torsional stress, untangle knots, and separate intertwined DNA molecules. They facilitate essential cellular processes such as DNA replication, transcription, recombination, and chromosome segregation by maintaining proper supercoiling and decatenation.

There are two main types. Type I topoisomerases cut one strand of the DNA duplex, changing the linking number by one per catalytic cycle, and reseal the strand without the need for ATP in the basic reaction (though some subtypes require energy for conformational steps). Type II topoisomerases cut both strands, pass another duplex through the break, and alter the linking number by two; this reaction is ATP-dependent. Type I executors are generally single-strand nicking enzymes, while Type II enzymes perform double-strand passage.

In bacteria, DNA gyrase is a type II topoisomerase that introduces negative supercoils, assisting transcription and replication, while topoisomerase IV primarily decatenates daughter chromosomes after replication. In eukaryotes, Topoisomerase I (Type IB) and Topoisomerase II (Type IIA) handle similar tasks, including decatenation during mitosis. Organellar genomes in mitochondria and chloroplasts also encode topoisomerases.

Topoisomerases are prominent drug targets. In cancer therapy, topo I inhibitors (such as camptothecin, irinotecan, and topotecan) and topo II inhibitors (such as doxorubicin and etoposide) disrupt enzyme-DNA complexes to kill proliferating cells. In bacteria, fluoroquinolones target DNA gyrase and topo IV, hindering replication. Given their essential roles in genome maintenance, topoisomerases are central to both basic biology and pharmacology.