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

48 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

Access to Document

10.1038/ncomms12059

Cite this

@article{34f9800a4307478e8c2ae49120db01cc,

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.",

author = "Midori Shimada and Takahiro Goshima and Hiromi Matsuo and Yoshikazu Johmura and Mayumi Haruta and Kazuhiro Murata and Hiromitsu Tanaka and Masahito Ikawa and Keiko Nakanishi and Makoto Nakanishi",

year = "2016",

month = jul,

day = "8",

doi = "10.1038/ncomms12059",

language = "English",

volume = "7",

journal = "Nature communications",

issn = "2041-1723",

publisher = "Nature Research",

}

TY - JOUR

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.

UR - https://www.scopus.com/pages/publications/84978128153

UR - https://www.scopus.com/inward/citedby.url?scp=84978128153&partnerID=8YFLogxK

U2 - 10.1038/ncomms12059

DO - 10.1038/ncomms12059

M3 - Article

C2 - 27389782

AN - SCOPUS:84978128153

SN - 2041-1723

VL - 7

JO - Nature communications

JF - Nature communications

M1 - 12059

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this