The kinetochore protein Bub1 participates in the DNA damage response. Academic Article uri icon

Overview

abstract

  • The DNA damage response (DDR) and the spindle assembly checkpoint (SAC) are two critical mechanisms by which mammalian cells maintain genome stability. There is a growing body of evidence that DDR elements and SAC components crosstalk. Here we report that Bub1 (budding uninhibited by benzimidazoles 1), one of the critical kinetochore proteins essential for SAC, is required for optimal DDRs. We found that knocking-down Bub1 resulted in prolonged H2AX foci and comet tail formation as well as hypersensitivity in response to ionizing radiation (IR). Further, we found that Bub1-mediated Histone H2A Threonine 121 phosphorylation was induced after IR in an ATM-dependent manner. We demonstrated that ATM phosphorylated Bub1 on serine 314 in response to DNA damage in vivo. Finally, we showed that ATM-mediated Bub1 serine 314 phosphorylation was required for IR-induced Bub1 activation and for the optimal DDR. Together, we elucidate the molecular mechanism of DNA damage-induced Bub1 activation and highlight a critical role of Bub1 in DDR.

publication date

  • November 9, 2011

Research

keywords

  • DNA Damage
  • Kinetochores
  • Protein Serine-Threonine Kinases

Identity

PubMed Central ID

  • PMC3758123

Scopus Document Identifier

  • 84855854958

Digital Object Identifier (DOI)

  • 10.1016/j.dnarep.2011.10.018

PubMed ID

  • 22071147

Additional Document Info

volume

  • 11

issue

  • 2