CENP-A Ubiquitylation Is Inherited through Dimerization between Cell Divisions

Yohei Niikura; Risa Kitagawa; Katsumi Kitagawa

doi:10.1016/j.celrep.2016.03.010

CENP-A Ubiquitylation Is Inherited through Dimerization between Cell Divisions

Yohei Niikura, Risa Kitagawa, Katsumi Kitagawa

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

The presence of chromatin containing the histone H3 variant CENP-A dictates the location of the centromere in a DNA sequence-independent manner. But the mechanism by which centromere inheritance occurs is largely unknown. We previously reported that CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. Here, we show that pre-existing ubiquitylated CENP-A is necessary for recruitment of newly synthesized CENP-A to the centromere and that CENP-A ubiquitylation is inherited between cell divisions. In vivo and in vitro analyses using dimerization mutants and dimerization domain fusion mutants revealed that the inheritance of CENP-A ubiquitylation requires CENP-A dimerization. Therefore, we propose models in which CENP-A ubiquitylation is inherited and, through dimerization, determines centromere location. Consistent with this model is our finding that overexpression of a monoubiquitin-fused CENP-A mutant induces neocentromeres at noncentromeric regions of chromosomes.

Original language	English (US)
Pages (from-to)	61-76
Number of pages	16
Journal	Cell Reports
Volume	15
Issue number	1
DOIs	https://doi.org/10.1016/j.celrep.2016.03.010
State	Published - Apr 5 2016
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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10.1016/j.celrep.2016.03.010

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@article{b526dc12f8e74fe799fbb3c78b637805,

title = "CENP-A Ubiquitylation Is Inherited through Dimerization between Cell Divisions",

abstract = "The presence of chromatin containing the histone H3 variant CENP-A dictates the location of the centromere in a DNA sequence-independent manner. But the mechanism by which centromere inheritance occurs is largely unknown. We previously reported that CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. Here, we show that pre-existing ubiquitylated CENP-A is necessary for recruitment of newly synthesized CENP-A to the centromere and that CENP-A ubiquitylation is inherited between cell divisions. In vivo and in vitro analyses using dimerization mutants and dimerization domain fusion mutants revealed that the inheritance of CENP-A ubiquitylation requires CENP-A dimerization. Therefore, we propose models in which CENP-A ubiquitylation is inherited and, through dimerization, determines centromere location. Consistent with this model is our finding that overexpression of a monoubiquitin-fused CENP-A mutant induces neocentromeres at noncentromeric regions of chromosomes.",

author = "Yohei Niikura and Risa Kitagawa and Katsumi Kitagawa",

note = "Funding Information: The authors thank Yue Xiong, Beezly Groh, Vivien Measday, Iain Cheeseman, Lars E.T. Jansen, Paul S. Maddox, Dorota Skowyra, Yoshinori Watanabe, Tatsuo Fukagawa, and past and current researchers at The Research Institute at Nationwide Children{\textquoteright}s Hospital and St. Jude Children{\textquoteright}s Research Hospital for their helpful discussion, experimental guidance, and reagents. The authors thank Don W. Cleveland, Daniele Fachinetti, Daniel R. Foltz, Gustavo W. Leone, John Thompson, Lawrence S. Kirschner, Amruta Ashtekar, Hitoshi Kurumizaka, Ben E. Black, and Glennis A. Logsdon for their generous gifts of reagents. This study was supported by NIH grants (GM68418) and CancerFree KIDS. Publisher Copyright: {\textcopyright} 2016 The Authors.",

year = "2016",

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doi = "10.1016/j.celrep.2016.03.010",

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AU - Niikura, Yohei

AU - Kitagawa, Risa

AU - Kitagawa, Katsumi

N1 - Funding Information: The authors thank Yue Xiong, Beezly Groh, Vivien Measday, Iain Cheeseman, Lars E.T. Jansen, Paul S. Maddox, Dorota Skowyra, Yoshinori Watanabe, Tatsuo Fukagawa, and past and current researchers at The Research Institute at Nationwide Children’s Hospital and St. Jude Children’s Research Hospital for their helpful discussion, experimental guidance, and reagents. The authors thank Don W. Cleveland, Daniele Fachinetti, Daniel R. Foltz, Gustavo W. Leone, John Thompson, Lawrence S. Kirschner, Amruta Ashtekar, Hitoshi Kurumizaka, Ben E. Black, and Glennis A. Logsdon for their generous gifts of reagents. This study was supported by NIH grants (GM68418) and CancerFree KIDS. Publisher Copyright: © 2016 The Authors.

PY - 2016/4/5

Y1 - 2016/4/5

N2 - The presence of chromatin containing the histone H3 variant CENP-A dictates the location of the centromere in a DNA sequence-independent manner. But the mechanism by which centromere inheritance occurs is largely unknown. We previously reported that CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. Here, we show that pre-existing ubiquitylated CENP-A is necessary for recruitment of newly synthesized CENP-A to the centromere and that CENP-A ubiquitylation is inherited between cell divisions. In vivo and in vitro analyses using dimerization mutants and dimerization domain fusion mutants revealed that the inheritance of CENP-A ubiquitylation requires CENP-A dimerization. Therefore, we propose models in which CENP-A ubiquitylation is inherited and, through dimerization, determines centromere location. Consistent with this model is our finding that overexpression of a monoubiquitin-fused CENP-A mutant induces neocentromeres at noncentromeric regions of chromosomes.

AB - The presence of chromatin containing the histone H3 variant CENP-A dictates the location of the centromere in a DNA sequence-independent manner. But the mechanism by which centromere inheritance occurs is largely unknown. We previously reported that CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. Here, we show that pre-existing ubiquitylated CENP-A is necessary for recruitment of newly synthesized CENP-A to the centromere and that CENP-A ubiquitylation is inherited between cell divisions. In vivo and in vitro analyses using dimerization mutants and dimerization domain fusion mutants revealed that the inheritance of CENP-A ubiquitylation requires CENP-A dimerization. Therefore, we propose models in which CENP-A ubiquitylation is inherited and, through dimerization, determines centromere location. Consistent with this model is our finding that overexpression of a monoubiquitin-fused CENP-A mutant induces neocentromeres at noncentromeric regions of chromosomes.

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CENP-A Ubiquitylation Is Inherited through Dimerization between Cell Divisions

Abstract

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