Interaction of BRCA1 with the DNA-Dependent Protein Kinase
Abstract
The DNA-dependent protein kinase (DNA-PK) plays a very important role in the repair of DNA double-strand breaks generated by ionizing radiation (IR). The activation of DNA-PK in response to IR involves multiple autophosphorylations at S/TQ residues of the catalytic subunit, DNA-Pkcs. We find that the activation of DNA-PKcs is attenuated during the S/G2 phases of the cell cycle, phases during which Brca1 is expressed. We found that DNA-Pkcs interacts with Brca1 and have mapped the interaction domain of Brca1. In order to investigate if the interaction of Brca1 with DNA-Pkcs might attenuate the activation of the letter, we examined DNA-PKcs autophosphorylation in Brca1-deficient HCC1937 cells ectopically expressing Brca1. We, however, failed to observe any significant differences in DNA-Pkcs autophosphorylation in the presence or absence of Brca1 in these cells. The lack of differences could be due to the low levels of Brca1 expression in these cells. Overexpression of the DNA-Pkcs-interaction domain of Brca1 might help to circumvent this problem.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2005
- Accession Number
- ADA486805
Entities
People
- Sandeep Burma
Organizations
- University of California, Berkeley