Journal
FEBS LETTERS
Volume 582, Issue 12, Pages 1700-1706Publisher
WILEY
DOI: 10.1016/j.febslet.2008.04.028
Keywords
double-strand DNA break (DSB); spindle assembly checkpoint (SAC); BubR1; prometaphase; kinetochore
Funding
- National Research Foundation of Korea [R11-2005-009-04003-0, 과06A1204] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Ask authors/readers for more resources
The effect of double-strand DNA breaks (DSBs) on the spindle assembly checkpoint (SAC) has important implications with respect to the relationship between SAC function and chromosome instability of cancer cells. Here, we demonstrate that induction of DSBs in mitosis results in prolonged hyper-phosphorylation of the SAC protein BubR1 and association of BubR1 with kinetochores in mammalian cells. Combining single cell time-lapse microscopy with immuno fluorescence, flow cytometry, and Western blot analysis in synchronized cells, we provide evidence that DSBs activate BubR1, leading to prometaphase arrest. Accordingly, elimination of BubR1 expression by siRNA resulted in the abrogation of mitotic delay in response to chromosome damage. These results suggest that BubR1 links DNA damage to kinetochore-associated SAC function. (C) 2008 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available