Deacetylase Activity Associates with Topoisomerase II and Is Necessary for Etoposide-induced Apoptosis

Colin A. Johnson, Kay Padget, Caroline A. Austin, Bryan M. Turner

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)

Abstract

DNA topoisomerase II (topo II) is a ubiquitous nuclear enzyme that is involved in DNA replication, transcription, chromosome segregation, and apoptosis. Here we show by immunoprecipitation, pull down with glutathioneS-transferase fusion proteins, and yeast two-hybrid analysis that both topo IIα and -β physically interact with the histone deacetylase HDAC1. The in vitro DNA decatenation activity of recombinant topo IIα and -β is inhibited by association with catalytically inactive, recombinant HDAC1. We provide evidence for the in vivo significance of the topo II-HDAC1 association, showing that inhibition of HDAC activity with trichostatin A suppresses apoptosis induced by the topo II poison etoposide, but not by the topoisomerase I inhibitor camptothecin. We suggest that chromatin remodeling by an HDAC-containing complex facilitates both topo II-catalyzed DNA rearrangement and etoposide-induced DNA damage in vivo.
Original languageEnglish
Pages (from-to)4539-4542
JournalJournal of Biological Chemistry
Volume276
Issue number7
DOIs
Publication statusPublished - 16 Feb 2001

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