title: A functional comparison of BRCA1 C-terminal domains in transcription activation and chromatin remodeling.
abstract: The BRCA1 C-terminal (BRCT) domain is present in a number of proteins that are involved in various aspects of chromosomal events. The BRCT domain of BRCA1 is important for its function in DNA repair and transcriptional activation. When tethered to chromosomal DNA, this region of BRCA1 is capable of inducing changes in chromatin structure. Despite the sequence homology and functional proximity shared by the BRCT-containing proteins, it is not clear whether different BRCT domains confer a common biochemical activity. Much less is known about the functional significance of the characteristic amino acid residues in the BRCT motif. Here, we show that chromatin remodeling and transcription activation is not a common feature of BRCT domains. However, the BRCT domain of the multi-functional repressor-activator protein 1 (RAP1) can activate transcription and remodel chromatin in a manner similar to that shown for the BRCA1 BRCT domain. Most of the conserved amino acid residues in the second BRCA1 BRCT domain are essential for its function in transcriptional activation. In contrast, mutations of many analogous amino acid residues in the RAP1 BRCT domain greatly elevate the transcriptional activity. These data indicate that the conserved residues in these two BRCT domains may play different roles in transcriptional activation.
authors.affiliation: Department of Biochemistry and Molecular Genetics, School of Medicine, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: T
authors.initials: T
authors.lastname: Miyake
authors.forename: Y F
authors.initials: YF
authors.lastname: Hu
authors.forename: D S
authors.initials: DS
authors.lastname: Yu
authors.forename: R
authors.initials: R
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism*; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017386:Sequence Homology, Amino Acid; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D019313:BRCA1 Protein; D002843:Chromatin