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Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis

Midori Shimada (), Takahiro Goshima, Hiromi Matsuo, Yoshikazu Johmura, Mayumi Haruta, Kazuhiro Murata, Hiromitsu Tanaka, Masahito Ikawa, Keiko Nakanishi and Makoto Nakanishi ()
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Midori Shimada: Graduate School of Medical Sciences, Nagoya City University
Takahiro Goshima: Graduate School of Medical Sciences, Nagoya City University
Hiromi Matsuo: Graduate School of Medical Sciences, Nagoya City University
Yoshikazu Johmura: Graduate School of Medical Sciences, Nagoya City University
Mayumi Haruta: Graduate School of Medical Sciences, Nagoya City University
Kazuhiro Murata: Graduate School of Medical Sciences, Nagoya City University
Hiromitsu Tanaka: Faculty of Pharmaceutical Sciences, Nagasaki International University, Sasebo
Masahito Ikawa: Research Institute for Microbial Diseases, Osaka University, Suita
Keiko Nakanishi: Institute for Developmental Research, Aichi Human Service Center
Makoto Nakanishi: Graduate School of Medical Sciences, Nagoya City University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract Proper deposition and activation of Aurora B at the centromere is critical for faithful chromosome segregation in mammals. However, the mechanistic basis for abrupt Aurora B kinase activation at the centromere has not yet been fully understood. We demonstrate here that Aurora B-mediated phosphorylation of histone H2AX at serine 121 (H2AX-pS121) promotes Aurora B autophosphorylation and is essential for proper chromosome segregation. Aurora B-mediated H2AX-pS121 is specifically detected at the centromere during mitosis. H2AX depletion results in a severe defect in activation and deposition of Aurora B at this locus. A phosphomimic mutant of H2AX at S121 interacts with activated Aurora B more efficiently than wild-type in vitro. Taken together, these results propose a model in which Aurora B-mediated H2AX-pS121 probably provide a platform for Aurora B autoactivation circuitry at centromeres and thus play a pivotal role in proper chromosome segregation.

Date: 2016
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DOI: 10.1038/ncomms12059

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