CENP-A K124Ubiquitylation Is Required for CENP-A Deposition at the Centromere

Yohei Niikura; Risa Kitagawa; Hiroo Ogi; Rashid Abdulle; Vishwajeeth Pagala; Katsumi Kitagawa

doi:10.1016/j.devcel.2015.01.024

CENP-A K124Ubiquitylation Is Required for CENP-A Deposition at the Centromere

Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Rashid Abdulle, Vishwajeeth Pagala, Katsumi Kitagawa

Resultado de la investigación: Article › revisión exhaustiva

71 Citas (Scopus)

Resumen

CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) andCENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that "signaling" ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.

Idioma original	English (US)
Páginas (desde-hasta)	589-603
Número de páginas	15
Publicación	Developmental Cell
Volumen	32
N.º	5
DOI	https://doi.org/10.1016/j.devcel.2015.01.024
Estado	Published - mar 9 2015
Publicado de forma externa	Sí

ASJC Scopus subject areas

Molecular Biology
Biochemistry, Genetics and Molecular Biology(all)
Developmental Biology
Cell Biology

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10.1016/j.devcel.2015.01.024

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title = "CENP-A K124Ubiquitylation Is Required for CENP-A Deposition at the Centromere",

abstract = "CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) andCENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that {"}signaling{"} ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.",

author = "Yohei Niikura and Risa Kitagawa and Hiroo Ogi and Rashid Abdulle and Vishwajeeth Pagala and Katsumi Kitagawa",

note = "Funding Information: The authors thank Yue Xiong, Beezly Groh, Vivien Measday, Iain Cheeseman, Lars E.T. Jansen, Paul S. Maddox, Mitsuhiro Yanagida, Dorota Skowyra, Yoshinori Watanabe, Tatsuo Fukugawa, Akira Kikuchi, Hiroyuki Suzuki, and past and current researchers at The Research Institute at Nationwide Children{\textquoteright}s Hospital and St. Jude Children{\textquoteright}s Research Hospital for helpful discussion, experimental guidance, and reagents; Don W. Cleveland, Ben E. Black, William C. Earnshaw, William R. Brinkley, Yue Xiong, Yi Zhang, Hengbin Wang, Pradip Raychaudhuri, Tom K. Kerppola, Yue Xiong, and Stephan Diekmann for their generous gifts of reagents. This study was supported by NIH grants GM68418. Publisher Copyright: {\textcopyright} 2015 Elsevier Inc.",

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AU - Niikura, Yohei

AU - Kitagawa, Risa

AU - Ogi, Hiroo

AU - Abdulle, Rashid

AU - Pagala, Vishwajeeth

AU - Kitagawa, Katsumi

N1 - Funding Information: The authors thank Yue Xiong, Beezly Groh, Vivien Measday, Iain Cheeseman, Lars E.T. Jansen, Paul S. Maddox, Mitsuhiro Yanagida, Dorota Skowyra, Yoshinori Watanabe, Tatsuo Fukugawa, Akira Kikuchi, Hiroyuki Suzuki, and past and current researchers at The Research Institute at Nationwide Children’s Hospital and St. Jude Children’s Research Hospital for helpful discussion, experimental guidance, and reagents; Don W. Cleveland, Ben E. Black, William C. Earnshaw, William R. Brinkley, Yue Xiong, Yi Zhang, Hengbin Wang, Pradip Raychaudhuri, Tom K. Kerppola, Yue Xiong, and Stephan Diekmann for their generous gifts of reagents. This study was supported by NIH grants GM68418. Publisher Copyright: © 2015 Elsevier Inc.

PY - 2015/3/9

Y1 - 2015/3/9

N2 - CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) andCENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that "signaling" ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.

AB - CENP-A is a centromere-specific histone H3 variant that epigenetically determines centromere identity to ensure kinetochore assembly and proper chromosome segregation, but the precise mechanism of its specific localization within centromeric heterochromatin remains obscure. We have discovered that CUL4A-RBX1-COPS8 E3 ligase activity is required for CENP-A ubiquitylation on lysine 124 (K124) andCENP-A centromere localization. A mutation of CENP-A, K124R, reduces interaction with HJURP (a CENP-A-specific histone chaperone) and abrogates localization of CENP-A to the centromere. Addition of monoubiquitin is sufficient to restore CENP-A K124R to centromeres and the interaction with HJURP, indicating that "signaling" ubiquitylation is required for CENP-A loading at centromeres. The CUL4A-RBX1 complex is required for loading newly synthesized CENP-A and maintaining preassembled CENP-A at centromeres. Thus, CENP-A K124R ubiquitylation, mediated by the CUL4A-RBX1-COPS8 complex, is essential for CENP-A deposition at the centromere.

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CENP-A K124Ubiquitylation Is Required for CENP-A Deposition at the Centromere

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