The ancestral role of ATP hydrolysis in type II topoisomerases: Prevention of DNA double-strand breaks

Andrew D. Bates, James M. Berger, Anthony Maxwell

Research output: Contribution to journalReview articlepeer-review

43 Scopus citations


Type II DNA topoisomerases (topos) catalyse changes in DNA topology by passing one doublestranded DNA segment through another. This reaction is essential to processes such as replication and transcription, but carries with it the inherent danger of permanent double-strand break (DSB) formation. All type II topos hydrolyse ATP during their reactions; however, only DNA gyrase is able to harness the free energy of hydrolysis to drive DNA supercoiling, an energetically unfavourable process. A long-standing puzzle has been to understand why the majority of type II enzymes consume ATP to support reactions that do not require a net energy input. While certain type II topos are known to 'simplify' distributions of DNA topoisomers below thermodynamic equilibrium levels, the energy required for this process is very low, suggesting that this behaviour is not the principal reason for ATP hydrolysis. Instead, we propose that the energy of ATP hydrolysis is needed to control the separation of protein-protein interfaces and prevent the accidental formation of potentially mutagenic or cytotoxic DSBs. This interpretation has parallels with the actions of a variety of molecular machines that catalyse the conformational rearrangement of biological macromolecules.

Original languageEnglish (US)
Pages (from-to)6327-6339
Number of pages13
JournalNucleic acids research
Issue number15
StatePublished - Aug 2011
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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