View : 23 Download: 0

Genome-wide screen of human bromodomain-containing proteins identifies Cecr2 as a novel DNA damage response protein

Title
Genome-wide screen of human bromodomain-containing proteins identifies Cecr2 as a novel DNA damage response protein
Authors
Lee S.-K.Park E.-J.Lee H.-S.Lee Y.S.Kwon J.
Ewha Authors
권종범
SCOPUS Author ID
권종범scopus
Issue Date
2012
Journal Title
Molecules and Cells
ISSN
1016-8478JCR Link
Citation
vol. 34, no. 1, pp. 85 - 91
Indexed
SCI; SCIE; SCOPUS; KCI WOS scopus
Abstract
The formation of γ-H2AX foci after DNA double strand breaks (DSBs) is crucial for the cellular response to this lethal DNA damage. We previously have shown that BRG1, a chromatin remodeling enzyme, facilitates DSB repair by stimulating γ-H2AX formation, and this function of BRG1 requires the binding of BRGI to acetylated histone H3 on γ-H2AX-containing nucleosomes using its bromodomain (BRD), a protein module that specifically recognizes acetyl-Lys moieties. We also have shown that the BRD of BRG1, when ectopically expressed in cells, functions as a dominant negative inhibitor of the BRG1 activity to stimulate γ-H2AX and DSB repair. Here, we found that BRDs from a select group of proteins have no such activity, suggesting that the γ-H2AX inhibition activity of BRG1 BRD is specific. This finding led us to search for more BRDs that exhibit γ-H2AX inhibition activity in the hope of finding additional BRD-containing proteins involved in DNA damage responses. We screened a total of 52 individual BRDs present in 38 human BRD-containing proteins, comprising 93% of all human BRDs. We identified the BRD of cat eye syndrome chromosome region candidate 2 (Cecr2), which recently was shown to form a novel chromatin remodeling complex with unknown cellular functions, as having a strong γ-H2AX inhibition activity. This activity of Cecr2 BRD is specific because it depends on the chromatin binding affinity of Cecr2 BRD. Small interfering RNA knockdown experiments showed that Cecr2 is important for γ-H2AX formation and DSB repair. Therefore, our genomewide screen identifies Cecr2 as a novel DNA damage response protein. © 2012 The Korean Society for Molecular and Cellular Biology and Springer Netherlands.
DOI
10.1007/s10059-012-0112-4
Appears in Collections:
자연과학대학 > 생명과학전공 > Journal papers
Files in This Item:
There are no files associated with this item.
Export
RIS (EndNote)
XLS (Excel)
XML


qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

BROWSE