TY - JOUR
T1 - Phospho-H2A and cohesin specify distinct tension-regulated sgo1 pools at kinetochores and inner centromeres
AU - Liu, Hong
AU - Jia, Luying
AU - Yu, Hongtao
N1 - Funding Information:
We thank Jungseog Kang for making the anti-H2A-pT120 antibody. This work was supported by grants from the Welch Foundation (I-1441) and the Cancer Prevention Research Institute of Texas (RP110465). H.Y. is an Investigator with the Howard Hughes Medical Institute.
PY - 2013/10/7
Y1 - 2013/10/7
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cub.2013.07.078
DO - 10.1016/j.cub.2013.07.078
M3 - Article
C2 - 24055156
AN - SCOPUS:84885325484
SN - 0960-9822
VL - 23
SP - 1927
EP - 1933
JO - Current Biology
JF - Current Biology
IS - 19
ER -