title: The kinetochore protein Bub1 participates in the DNA damage response.
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.
authors.affiliation: Department of Radiation Oncology, The Methodist Hospital Research Institute, 6670 Bertner Avenue, Houston, TX 77030, USA.
authors.forename: Chunying
authors.initials: C
authors.lastname: Yang
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Yiran
authors.initials: Y
authors.lastname: Xu
authors.forename: Kathryn L
authors.initials: KL
authors.lastname: Brinkman
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Ishiyama
authors.forename: Stephen T C
authors.initials: ST
authors.lastname: Wong
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
mesh_terms: D000595:Amino Acid Sequence; D064007:Ataxia Telangiectasia Mutated Proteins; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018386:Kinetochores / Q000378:metabolism* / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects; D008969:Molecular Sequence Data; D010766:Phosphorylation / Q000528:radiation effects; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011836:Radiation Tolerance; D013912:Threonine / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D006657:Histones; D025521:Tumor Suppressor Proteins; D013912:Threonine; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases
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