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; Makoto Nakanishi

doi:10.1038/ncomms12059

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, Makoto Nakanishi

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

46 Citations (Scopus)

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.

Original language	English
Article number	12059
Journal	Nature communications
Volume	7
DOIs	https://doi.org/10.1038/ncomms12059
Publication status	Published - 08-07-2016
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Chemistry
General Biochemistry,Genetics and Molecular Biology
General Physics and Astronomy

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10.1038/ncomms12059

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title = "Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis",

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.",

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T1 - Essential role of autoactivation circuitry on Aurora B-mediated H2AX-pS121 in mitosis

AU - Shimada, Midori

AU - Goshima, Takahiro

AU - Matsuo, Hiromi

AU - Johmura, Yoshikazu

AU - Haruta, Mayumi

AU - Murata, Kazuhiro

AU - Tanaka, Hiromitsu

AU - Ikawa, Masahito

AU - Nakanishi, Keiko

AU - Nakanishi, Makoto

PY - 2016/7/8

Y1 - 2016/7/8

N2 - 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.

AB - 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.

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

Abstract

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