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

Lookup NU author(s): Dr Kay Padget, Emerita Professor Caroline AustinORCiD

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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 II alpha and -beta physically interact with the histone deacetylase HDAC1. The in vitro DNA decatenation activity of recombinant topo II alpha 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.

Publication metadata

Author(s): Austin CA; Padget K; Johnson CA; Turner BM

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2001

Volume: 276

Issue: 7

Pages: 4539-4542

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.C000824200

DOI: 10.1074/jbc.C000824200

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