TY - JOUR
T1 - Deacetylase activity associates with topoisomerase II and is necessary for etoposide-induced apoptosis
AU - Johnson, Colin
AU - Padget, K
AU - Austin, CA
AU - Turner, Bryan
PY - 2001/2/9
Y1 - 2001/2/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0035895909&partnerID=8YFLogxK
U2 - 10.1074/jbc.C000824200
DO - 10.1074/jbc.C000824200
M3 - Article
C2 - 11136718
SN - 1083-351X
VL - 276
SP - 4539
EP - 4542
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 7
ER -