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

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.
Mesh Terms:
Apoptosis, DNA Topoisomerases, Type II, Enzyme Inhibitors, Etoposide, HL-60 Cells, Hela Cells, Histone Deacetylase 1, Histone Deacetylase Inhibitors, Histone Deacetylases, Humans, Hydroxamic Acids, Precipitin Tests, Two-Hybrid System Techniques
J. Biol. Chem.
Date: Feb. 16, 2001
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