Kinetics of BRCA1 regulation in response to UVC radiation |
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| Authors: | Clarkin C E Zhang H Weber B L |
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| Institution: | (1) Department of Biochemistry and Molecular Biophysics, University of Pennsylvania, Philadelphia (Pennsylvania 19104, USA), US;(2) Department of Medicine, University of Pennsylvania, Philadelphia (Pennsylvania 19104, USA), Fax +1 215 573 2486, e-mail: weberb@mail.med.upenn.edu, US;(3) Department of Genetics, University of Pennsylvania, Philadelphia (Pennsylvania 19104, USA), US |
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| Abstract: | To investigate changes in BRCA1 following DNA damage, we exposed MCF-7 cells to increasing doses of ultraviolet C. We observed
an increase in BRCA1 protein levels above 78 J/m2. This increase was observed as early as 5 min after irradiation. BRCA1 levels were then observed to decrease after 2 h, consistent
with the previously published data. By pretreating with cycloheximide prior to irradiation, we observed a decrease in the
protein half-life, from 3.5 h to 53 min, suggesting that a decrease in protein half-life may cause the lower levels of BRCA1
after irradiation. We also observed an increase in BRCA1 mRNA within 15 min of irradiation, followed by a decrease after 4
h. These data suggest that newly translated protein may contribute to increases in BRCA1 protein levels. The very rapid changes
in BRCA1 support its role as a sensor of DNA damage, as opposed to being a repair gene.
Received 6 April 2000; received after revision 23 May 2000; accepted 23 May 2000 |
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| Keywords: | , Breast cancer, BRCA1, DNA damage, ultraviolet C, MCF-7, |
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