HMGB1 interacts with human topoisomerase II alpha and stimulates its catalytic activity

摘要

DNA topoisomerase II alpha ( topo II alpha) is an essential nuclear enzyme and its unique decatenation activity has been implicated in many aspects of chromosome dynamics such as chromosome replication and segregation during mitosis. Here we show that chromatin-associated protein HMGB1 ( a member of the large family of HMG-box proteins with possible functions in DNA replication, transcription, recombination and DNA repair) promotes topo II alpha-mediated catenation of circular DNA, relaxation of negatively supercoiled DNA and decatenation of kinetoplast DNA. HMGB1 interacts with topo IIa and this interaction, like the stimulation of the catalytic activity of the enzyme, requires both HMG-box domains of HMGB1. A mutant of HMGB1, which cannot change DNA topology stimulates DNA decatenation by topo IIa indistinguishably from the wild-type protein. Although HMGB1 stimulates ATP hydrolysis by topo IIa, the DNA cleavage is much more enhanced. The observed abilities of HMGB1 to interact with topo IIa and promote topo IIa binding to DNA suggest a mechanism by which HMGB1 stimulates the catalytic activity of the enzyme via enhancement of DNA cleavage.