Chromatin remodeling and activation of chromosomal DNA replication by an acidic transcriptional activation domain from BRCA1.
An increasing number of transcription factors have been shown to activate DNA replication. However, the underlying mechanism remains to be elucidated. Here it is shown that when tethered to a cellular replication origin, the acidic transcriptional activation domain of the breast cancer protein BRCA1 alters the local chromatin structure and stimulates chromosomal DNA replication. Cancer-predisposing mutations in BRCA1 that abolish transcriptional activation also prevent chromatin remodeling and activation of replication. Chromatin remodeling occurs even in the absence of a functional replication origin. Thus, increasing chromatin accessibility may be an important mechanism used by transcription factors to facilitate multiple nuclear processes.
Hu
Y F
YF
Department of Biochemistry and Molecular Genetics, Health Sciences Center, University of Virginia, Charlottesville, Virginia 22908, USA.
Hao
Z L
ZL
Li
R
R
D019313:BRCA1 Protein / Q000235:genetics*; D002843:Chromatin / Q000235:genetics*; D015825:Chromosomes, Fungal; D004261:DNA Replication / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D015533:Transcriptional Activation
D019313:BRCA1 Protein; D002843:Chromatin