PMID:24055156

Citation	Liu, H, Jia, L and Yu, H' (2013) Phospho-H2A and Cohesin Specify Distinct Tension-Regulated Sgo1 Pools at Kinetochores and Inner Centromeres. Curr. Biol. '
Abstract	Accurate chromosome segregation requires coordination between the dissolution of sister-chromatid cohesion and the establishment of proper kinetochore-microtubule attachment [1-6]. During mitosis, sister-chromatid cohesion at centromeres enables the biorientation of and tension across sister kinetochores. The complex between shugoshin and protein phosphatase 2A (Sgo1-PP2A) localizes to centromeres in mitosis [7-10], binds to cohesin in a reaction requiring Cdk-dependent phosphorylation of Sgo1 [11], dephosphorylates cohesin-bound sororin [11], and protects a centromeric pool of cohesin from mitotic kinases and the cohesin inhibitor Wapl [11-14]. Cleavage of centromeric cohesin by separase allows sister chromatids connected to microtubules from opposing poles to be evenly partitioned into daughter cells [15, 16]. The centromeric localization of Sgo1 requires histone H2A phosphorylation at T120 (H2A-pT120) by the kinase Bub1 [17-19]. The exact role of H2A-pT120 in Sgo1 regulation is, however, unclear. Here, we show that cohesin and H2A-pT120 specify two distinct pools of Sgo1-P2A at inner centromeres and kinetochores, respectively, in human cells. Bub1 inactivation delocalizes cohesin-Sgo1 to chromosome arms. Kinetochore tension triggers Sgo1 dephosphorylation and redistributes Sgo1 from inner centromeres to kinetochores. Incomplete Sgo1 redistribution causes chromosome nondisjunction. Our study suggests that Bub1-mediated H2A phosphorylation penetrates kinetochores and that this histone mark contributes to a tension-sensitive Sgo1-based molecular switch for chromosome segregation.
Links	PubMed Online version:10.1016/j.cub.2013.07.078
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:BUB1	part_of	GO:0000942: condensed nuclear chromosome outer kinetochore	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete
HUMAN:BUB1		GO:0000942: condensed nuclear chromosome outer kinetochore	ECO:0000314:		C		Figure S1A. The authors state that "Sgo1 and Bub1 localized to inner centromeres and outer kinetochores, respectively.	complete CACAO 8644
HUMAN:SGOL1		GO:0000775: chromosome, centromeric region	ECO:0000314:		C		Figure 1A	complete CACAO 8642
HUMAN:SGOL1	part_of	GO:0000775: chromosome, centromeric region	ECO:0000314: direct assay evidence used in manual assertion		C		Seeded From UniProt	complete

References

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