Aurora-B mediated ATM serine 1403 phosphorylation is required for mitotic ATM activation and the spindle checkpoint. Academic Article uri icon

Overview

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.

publication date

  • November 18, 2011

Research

keywords

  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Genome, Human
  • Genomic Instability
  • Kinetochores
  • Mitosis
  • Protein Serine-Threonine Kinases
  • Spindle Apparatus
  • Tumor Suppressor Proteins

Identity

PubMed Central ID

  • PMC3228519

Scopus Document Identifier

  • 81355164085

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2011.09.016

PubMed ID

  • 22099307

Additional Document Info

volume

  • 44

issue

  • 4