Aurora-B Mediated ATM Serine 1403 Phosphorylation Is Required for Mitotic ATM Activation and the Spindle Checkpoint

Chunying Yang, Xi Tang, Xiaojing Guo, Yohei Niikura, Katsumi Kitagawa, Kemi Cui, Stephen T.C. Wong, Li Fu, Bo Xu

Research output: Contribution to journalArticle

71 Scopus citations

Abstract

The ATM kinase plays a critical role in the maintenance of genetic stability. ATM is activated in response to DNA damage and is essential for cell-cycle checkpoints. Here, we report that ATM is activated in mitosis in the absence of DNA damage. We demonstrate that mitotic ATM activation is dependent on the Aurora-B kinase and that Aurora-B phosphorylates ATM on serine 1403. This phosphorylation event is required for mitotic ATM activation. Further, we show that loss of ATM function results in shortened mitotic timing and a defective spindle checkpoint, and that abrogation of ATM Ser1403 phosphorylation leads to this spindle checkpoint defect. We also demonstrate that mitotically activated ATM phosphorylates Bub1, a critical kinetochore protein, on Ser314. ATM-mediated Bub1 Ser314 phosphorylation is required for Bub1 activity and is essential for the activation of the spindle checkpoint. Collectively, our data highlight mechanisms of a critical function of ATM in mitosis.

Original languageEnglish (US)
Pages (from-to)597-608
Number of pages12
JournalMolecular Cell
Volume44
Issue number4
DOIs
StatePublished - Nov 18 2011
Externally publishedYes

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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