BRCA2 and Genome Integrity

Abstract

Abstract : The BRCA2 tumor suppressor gene has been suggested to play an important role in DNA repair and maintaining genome integrity. Most evidences supporting this hypothesis, however, were obtained from studying mouse embryonic stem cells or embryonic fibroblast. The importance of BRCA2 in maintaining genome integrity in human cells is not very clear. We have completed the Task 1, generation of Capan- 1 derivatives that conditionally express wild type BRCA2. Capan-1 is the only human cell lines known to not express wild type BRCA2. We have obtained two Capan-1 derivatives that express exogenous wild type BRCA2 under the regulation of tetracycline. We have also obtained several Capan- 1 derivatives that express exogenous mutant BRCA2, either constitutively or regulated by tetracycline. We have also carried out the first part of the Task 3, characterization of Capan-i derivatives to genotoxic agents. We examined the sensitivity of wild type BRCA2- expressing Capan-1 derivatives to ionizing radiation and DNA damaging chemicals. Our preliminary results showed that there was no detectable difference in the sensitivity to these treatments between when these cells expressed or did not express the wild type BRCA2.