DTIC ADA436963: Phosphorylation of hRad17 by atr is Required for Ce... | |
by Defense Technical Information Center | |
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Targeted protein phosphorylation is a key event that | |
serves to transduce DNA damage- induced cell signals from | |
upstream sensors to downstream effectors. ATR kinase | |
phosphorylates BRCA1 and Rad17 upon DNA damage. As a | |
first approach to evaluate the functional consequence of | |
IR-induced site-specifically phosphorylated residues on | |
BRCA1, -we have established a BRCA1-dependent | |
transcription-based assay which assesses the BRCA1- | |
dependent repression function of ZBRK1 in mammalian cell | |
from a reporter template bearing ZBRK1 DNA-binding sites. | |
I found that ZBRK1 formed a homo-tetramer on the target | |
gene promoter functioning as a DNA-binding dependent | |
repressor as well as a DNA-binding independent | |
corepressor. Functional dissection of ZBRK1 led to | |
identification and characterization of a novel BRCA1- | |
dependent repression domain encompassing ZBRK1 zinc | |
fingers 5-8 and the unique C-terminus. This C-terminal | |
repression domain functions in a BRCA1-dependent, histone | |
deactylase-dependent and promoter-specific manner. | |
Significantly, BRCA1 mediates ZBRK1 transcriptional | |
repression function by modulating- two properties of | |
ZBRK1 as a transcription factor: its DNA-binding and the | |
recruitment of other co-repressor proteins. BRCA1- | |
dependent ZBRK1 repression assay may now be' exploited to | |
evaluate the influence of IR-induced site-specific | |
phosphorylation of BRCA1 on its sequence-specific co- | |
repressor function. | |
Date Published: 2018-05-27 11:16:43 | |
Identifier: DTIC_ADA436963 | |
Item Size: 37934215 | |
Language: english | |
Media Type: texts | |
# Topics | |
DTIC Archive; Tan, Wei; TEXAS UNIV HE... | |
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# Uploaded by | |
@chris85 | |
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