Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 651-664 |
| Number of pages | 14 |
| Journal | Journal of Cell Biology |
| Volume | 213 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jan 1 2016 |
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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 L; Mukherjee, Soumya R; Chacon, Jeremy M; Bachant, Jeff; Gardner, Melissa K; Clarke, Duncan J.
In: Journal of Cell Biology, Vol. 213, No. 6, 01.01.2016, p. 651-664.Research output: Contribution to journal › Article
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TY - JOUR
T1 - A noncatalytic function of the topoisomerase II CTD in Aurora B recruitment to inner centromeres during mitosis
AU - Edgerton, Heather
AU - Johansson, Marnie
AU - Keifenheim, Daniel L
AU - Mukherjee, Soumya R
AU - Chacon, Jeremy M
AU - Bachant, Jeff
AU - Gardner, Melissa K
AU - Clarke, Duncan J
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84975461818&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84975461818&partnerID=8YFLogxK
U2 - 10.1083/jcb.201511080
DO - 10.1083/jcb.201511080
M3 - Article
C2 - 27325791
AN - SCOPUS:84975461818
VL - 213
SP - 651
EP - 664
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 6
ER -