Nuclear Dynamics of BRCA1-Dependent Transcription Regulation
Abstract
BRCA1 coordinates cellular responses to DNA damage. It functions as a co-repressor of GADD45aand estrogen-responsive transcription through interactions with a DNA-binding protein termedZBRK1. Our goal is to develop a biosensor system to visualize transcription control by ZBRK1 and BRCA1 in single living andlor fixed cells. The rationale is to use integrated DNA bindingsites to obtain real time, multiplex-based data. The reportable outcomes for the period are:1) UAS and ZRE array-bearing plasmids have been constructed; 2) Transient and stable reporterexpression have been demonstrated; 3) Stable cell lines with G20, G40 and Z32 are on line forstudies; 4) Construction of fluorescent GAL4-DBD and ZBRK1 fusion protein has been achieved, and BRCA1 derivatives are in progress; 5) Development of a high throughput screening system for estrogen receptor activated transcription complex. When operational, these systems will document real time nuclear dynamics of ZBRK1/BRCA1-dependent chromatin modification systems,as cells mount transcriptional responses to genotoxins and identify BRCA1-associated proteinsthat mediate its actions.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2006
- Accession Number
- ADA463827
Entities
People
- Zelton D. Sharp
Organizations
- University of Texas Health Science Center at San Antonio