Accession Number : ADA463242


Title :   Tumor Suppression by BRCA-1: A Critical Role at DNA Replication Forks


Descriptive Note : Final rept. 15 Sep 2005-14 Sep 2006


Corporate Author : COLUMBIA UNIV NEW YORK


Personal Author(s) : Gautier, Jean


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/a463242.pdf


Report Date : Oct 2006


Pagination or Media Count : 7


Abstract : BRCA1 is the major breast cancer susceptibility gene. It forms heterodimers with BARD1. Inactivation of either gene results in identical phenotypes suggesting that these proteins function primarily as a complex. BRCA1 deficiencies are associated with cellular phenotypes consistent with a DNA replication defect. We wished to test the hypothesis that BRCA1/BARD1 function during DNA replication supporting DNA transactions at replication forks. We are using cell-free extracts derived from Xenopus laevis eggs that support: 1. Semi-conservative, cell-cycle regulated DNA replication; 2. Many facets of the DNA damage response. Our key accomplishments were to generate specific antibodies against Xenopus BARD1 and BRCA1. We also demonstrate that the complex assembles to chromatin in a DNA replication-dependent manner. Finally, we show that BRCA1/BARD1 loading to chromatin does not dramatically increases following DNA damage, suggesting that it might be relocalized within chromatin compartments.


Descriptors :   *DEOXYRIBONUCLEIC ACIDS , *GENES , *BREAST CANCER , FUNCTIONS , DAMAGE , RESPONSE , CHROMATIN , HYPOTHESES , ANTIBODIES , PROTEINS , COMPARTMENTS


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


Distribution Statement : APPROVED FOR PUBLIC RELEASE