topoisomeraz

Topoisomeraz, commonly written as topoisomerase, refers to a family of enzymes that regulate the topology of DNA. They achieve this by creating transient breaks in the DNA backbone to add or remove supercoils, relieving torsional stress generated during replication, transcription, recombination, and chromatin remodeling. Topoisomerases are essential for proper DNA metabolism and chromosome maintenance, and they are found in all domains of life. They are traditionally classified into two main types, based on their mechanism and the number of DNA strands they cut.

Type I topoisomerases cut a single strand of DNA and change the linking number by increments of one per catalytic cycle. They do not require ATP for strand passage, though some subtypes use energy indirectly. Type IA and Type IB are subfamilies with different modes of strand passage and preferences for relaxing supercoils. Type II topoisomerases cut both strands of DNA and require ATP to power strand passage, changing the linking number by two. Bacterial DNA gyrase (a type II enzyme) can introduce negative supercoils, while other type II enzymes primarily decatenate and help in chromosome condensation.

Biological roles include enabling smooth progression of replication forks, aiding transcription by removing supercoils ahead of RNA polymerase, and organizing chromatin in eukaryotes. In mitosis, type II topoisomerases assist in chromosome decatenation and segregation. Inhibitors targeting topoisomerases have clinical importance: fluoroquinolone antibiotics inhibit bacterial gyrase and topo IV, whereas certain anticancer drugs (for example, etoposide and doxorubicin) trap topo II-DNA intermediates, causing DNA damage in cancer cells.

Overall, topoisomeraz/topoisomerases are central to maintaining DNA topology and genome stability across organisms.