A novel chromatin tether domain controls topoisomerase IIα dynamics and mitotic chromosome formation.
DNA topoisomerase IIα (Topo IIα) is the target of an important class of anticancer drugs, but tumor cells can become resistant by reducing the association of the enzyme with chromosomes. Here we describe a critical mechanism of chromatin recruitment and exchange that relies on a novel chromatin tether (ChT) domain and mediates interaction with histone H3 and DNA. We show that the ChT domain controls the residence time of Topo IIα on chromatin in mitosis and is necessary for the formation of mitotic chromosomes. Our data suggest that the dynamics of Topo IIα on chromosomes are important for successful mitosis and implicate histone tail posttranslational modifications in regulating Topo IIα.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, MN 55455.
Andrew B
AB
Lane
Juan F
JF
Giménez-Abián
Duncan J
DJ
Clarke
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000378:metabolism*; D002875:Chromosomes / Q000235:genetics; D004247:DNA / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D008938:Mitosis / Q000235:genetics*; D018668:Muntjacs / Q000235:genetics; D009685:Nuclear Envelope / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins / Q000235:genetics
D000951:Antigens, Neoplasm; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D020033:Protein Isoforms; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D004247:DNA; D004250:DNA Topoisomerases, Type II