decatenating

Decatenating is the process of separating interlinked DNA molecules, known as catenanes, that arise as a byproduct of DNA replication. This entanglement is common when circular genomes, such as many bacterial chromosomes and plasmids, are replicated, and it must be resolved to allow proper chromosome or plasmid segregation into daughter cells.

The task is carried out primarily by type II DNA topoisomerases. These enzymes introduce transient double-strand breaks in one DNA duplex, pass another duplex through the break, and reseal the breaks. Each catalytic cycle can change the linking number by two, and ATP hydrolysis provides the energy required for strand passage. In bacteria, decatenation is mainly performed by topoisomerase IV; in eukaryotes, Topo IIα and Topo IIβ carry out decatenation during mitosis, coordinating with chromosome condensation and sister-chromatid separation.

Biological significance is high, as decatenation is essential for proper chromosome and plasmid segregation. When catenanes persist, daughter DNAs or chromosomes may fail to separate correctly, leading to genomic instability or cell division defects. In bacteria, decatenation is part of a network of processes that ensure complete genome partitioning before cell division.

Clinical relevance lies in the use of topoisomerase II inhibitors as chemotherapeutic agents. Drugs such as doxorubicin, daunorubicin, and etoposide disrupt decatenation by stabilizing the enzyme-DNA complex, producing DNA breaks and promoting cancer cell death.