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

Department of Radiation Oncology, The Methodist Hospital Research Institute, Weill Cornell Medical College, Houston, TX 77030, USA.

Molecular cell 2011 Nov 18

filter terms:

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. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Chunying Yang, Xi Tang, Xiaojing Guo, Yohei Niikura, Katsumi Kitagawa, Kemi Cui, Stephen T C Wong, Li Fu, Bo Xu. Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint. Molecular cell. 2011 Nov 18;44(4):597-608