title: Primary structure-based function characterization of BRCT domain replicates in BRCA1.
abstract: BRCA1 is a large protein that exhibits a multiplicity of functions in its apparent role in DNA repair. Certain mutations of BRCA1 are known to have exceptionally high penetrance with respect to familial breast and ovarian cancers. The structures of the N-terminus and C-terminus of the protein have been determined. The C-terminus unit consists of two alpha-beta-alpha domains designated BRCT. We predicated two homologous BRCT regions in the BRCA1 internal region, and subsequently produced and purified these protein domains. Both recombinant domains show significant self-association capabilities as well as a preferential tendency to interact with each other. These results suggest a possible regulatory mechanism for BRCA1 function. We have demonstrated p53-binding activity by an additional region, and confirmed previous results showing that two regions of BRCA1 protein bind p53 in vitro. Based on sequence analysis, we predict five p53-binding sites. Our comparison of binding by wild-type and mutant domains indicates the sequence specificity of BRCA1-p53 interaction.
authors: Center for Clinical Cancer Genetics, University of Chicago Medical Center, Chicago, IL 60637, USA.
authors: Yinghua
authors: Y
authors: Chen
authors: Stanley
authors: S
authors: Borowicz
authors: James
authors: J
authors: Fackenthal
authors: Frank R
authors: FR
authors: Collart
authors: Elizabeth
authors: E
authors: Myatt
authors: Shiu
authors: S
authors: Moy
authors: Gyorgy
authors: G
authors: Babnigg
authors: Rosemarie
authors: R
authors: Wilton
authors: William E
authors: WE
authors: Boernke
authors: Marianne
authors: M
authors: Schiffer
authors: Fred J
authors: FJ
authors: Stevens
authors: Olufunmilayo I
authors: OI
authors: Olopade