کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1980386 1061849 2012 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
The kinetochore protein Bub1 participates in the DNA damage response
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
The kinetochore protein Bub1 participates in the DNA damage response
چکیده انگلیسی

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.


► Bub1 is required for the DNA damage response.
► ATM phosphorylates Bub1 on Serine 214 in response to ionizing irradiation.
► ATM-mediated Bub1 phosphorylation is essential for optimal DNA damage responses.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 11, Issue 2, 1 February 2012, Pages 185–191
نویسندگان
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