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A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis.

Edgerton, Heather; Johansson, Marnie; Keifenheim, Daniel; Mukherjee, Soumya; Chacón, Jeremy M; Bachant, Jeff; Gardner, Melissa K; Clarke, Duncan J.
J Cell Biol; 213(6): 651-64, 2016 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-27325791
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.
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