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Chromatin Remodeling Function of BRCA1 and its Implication in Regulation of DNA Replication

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Annual rept. 1 Sep 1999-31 Aug 2000

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The BRCAl C-Terminal BRCT domain is present in a number of proteins that are involved in various aspects of chromosomal events. The BRCT domain of BRCAl is important for BRCAl function in DNA repair and transcriptional activation. When tethered to chromosomal DNA, this region of BRCAl is capable of inducing changes in chromatin structure. Despite the sequence homology and functional proximity shared by the BRCT-containing proteins, it is not known whether different BRCT domains confer a common biochemical activity. Mere we show that the BRCT domain of the Saccharoinyces cerevisiae RAPl scRAP I, but not the other yeast BRCT domains tested, is capable of activating transcription and remodeling chromatin in a manner similar to that shown for the BRCT domain of BRCAl. A number of the highly conserved amino acid residues in the BRCT domains of RAP1 and BRCAl are critical for their activities in yeast and human cells, respectively. Our work also reveals a region in the scRAPl BRCT domain that negatively regulates its transcriptional activity. We suggest that chromatin remodeling is an important feature shared by a subset of the BRCT family members to facilitate multiple chromosomal events.

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  • Anatomy and Physiology
  • Medicine and Medical Research

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