A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis.
Faithful chromosome segregation depends on the precise timing of chromatid separation, which is enforced by checkpoint signals generated at kinetochores. Here, we provide evidence that the C-terminal domain (CTD) of DNA topoisomerase IIα (Topo II) provides a novel function at inner centromeres of kinetochores in mitosis. We find that the yeast CTD is required for recruitment of the tension checkpoint kinase Ipl1/Aurora B to inner centromeres in metaphase but is not required in interphase. Conserved CTD SUMOylation sites are required for Ipl1 recruitment. This inner-centromere CTD function is distinct from the catalytic activity of Topo II. Genetic and biochemical evidence suggests that Topo II recruits Ipl1 via the Haspin-histone H3 threonine 3 phosphorylation pathway. Finally, Topo II and Sgo1 are equally important for Ipl1 recruitment to inner centromeres. This indicates H3 T3-Phos/H2A T120-Phos is a universal epigenetic signature that defines the eukaryotic inner centromere and provides the binding site for Ipl1/Aurora B.
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Heather
0000-0003-3578-6704
H
Edgerton
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Marnie
M
Johansson
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Daniel
D
Keifenheim
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Soumya
0000-0003-3040-4658
S
Mukherjee
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Jeremy M
JM
Chacón
Department of Cell Biology and Neuroscience, University of California, Riverside, Riverside, CA 92521.
Jeff
J
Bachant
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455.
Melissa K
MK
Gardner
Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455 clark140@umn.edu.
Duncan J
0000-0002-7795-3294
DJ
Clarke
D000951:Antigens, Neoplasm / Q000378:metabolism*; D064107:Aurora Kinase B / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002503:Centromere / Q000378:metabolism* / Q000502:physiology*; D002842:Chromatids / Q000378:metabolism; D020090:Chromosome Segregation / Q000502:physiology; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005656:Fungal Proteins / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018386:Kinetochores / Q000378:metabolism / Q000502:physiology; D008677:Metaphase / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D058207:Sumoylation / Q000502:physiology; D015003:Yeasts / Q000378:metabolism / Q000502:physiology
D000951:Antigens, Neoplasm; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; D006657:Histones; D064107:Aurora Kinase B; D017346:Protein Serine-Threonine Kinases; D004250:DNA Topoisomerases, Type II