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J Biol Chem. 2001 Feb 16;276(7):4539-42. Epub 2001 Jan 2.

Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis.

Author information

1
Chromatin and Gene Expression Group, Department of Anatomy, University of Birmingham Medical School, Birmingham B15 2TT, United Kingdom.

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 glutathione S-transferase fusion proteins, and yeast two-hybrid analysis that both topo IIalpha and -beta physically interact with the histone deacetylase HDAC1. The in vitro DNA decatenation activity of recombinant topo IIalpha and -beta 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.

PMID:
11136718
DOI:
10.1074/jbc.C000824200
[Indexed for MEDLINE]
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