Accession Number : ADA432142


Title :   Interaction of BRCA1 With the DNA-Dependent Protein Kinase


Descriptive Note : Annual rept. 18 Aug 2003-17 Aug 2004


Corporate Author : CALIFORNIA UNIV BERKELEY


Personal Author(s) : Burma, Sandeep


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a432142.pdf


Report Date : Sep 2004


Pagination or Media Count : 34


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 SftQ 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 the tumor suppressor protein Brca1 is expressed. We found that DNA-PKcs interacts with Brcal and have mapped the DNA-PKcs-interaction domain of Brca1. In order to investigate if the interaction of Brcai with DNA-PKcs might attenuate DNA-Pkcs activation, we examined DNA-PKcs autophosphorylation in Brca1-deficient HCC1937 cells ectopically expressing Brca1. Although we did not observe any significant differences in DNA-PKcs autophosphorylation in the presence or absence of Brca1, the lack of observable differences could also be due to the low levels of Brca1 expression in these cells. We are currently attempting to overexpress the DNA-PK-interaction domain of Brca1 in human cells to see if this region of Brcal has any effect on DNA-PK activation. We are also examining if the interaction of DNA-PK with Brca1 has any modulatory effect on Ercal phosphorylation in response to IR.


Descriptors :   *PROTEINS , *DEOXYRIBONUCLEIC ACIDS , *CELLS(BIOLOGY) , *IONIZING RADIATION , *BREAST CANCER , ACTIVATION , REPAIR , GENES , PHOSPHORYLATION , PHOSPHORUS TRANSFERASES


Subject Categories : Genetic Engineering and Molecular Biology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE