The kinetochore protein Bub1 participates in the DNA damage response

Chunying Yang, Haibo Wang, Yiran Xu, Kathryn L. Brinkman, Hiromichi Ishiyama, Stephen T.C. Wong, Bo Xu

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)185-191
Number of pages7
JournalDNA Repair
Volume11
Issue number2
DOIs
StatePublished - Feb 1 2012

Keywords

  • ATM
  • Bub1
  • DNA damage response

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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