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Mol. Cells 2012; 34(1): 85-91

Published online June 12, 2012

https://doi.org/10.1007/s10059-012-0112-4

© The Korean Society for Molecular and Cellular Biology

Genome-Wide Screen of Human Bromodomain-Containing Proteins Identifies Cecr2 as a Novel DNA Damage Response Protein

Seul-Ki Lee1, Eun-Jung Park1, Han-Sae Lee, Ye Seul Lee, and Jongbum Kwon*

Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea, 1These authors contributed equally to this work.

Correspondence to : *Correspondence: jongkwon@ewha.ac.kr

Received: April 16, 2012; Accepted: May 2, 2012

Abstract

The formation of ?-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 ?-H2AX formation, and this function of BRG1 requires the binding of BRGI to acetylated histone H3 on ?-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 ?-H2AX and DSB repair. Here, we found that BRDs from a select group of proteins have no such activity, suggesting that the ?-H2AX inhibition activity of BRG1 BRD is specific. This finding led us to search for more BRDs that exhibit ?-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 ?-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 ?-H2AX formation and DSB repair. Therefore, our genome-wide screen identifies Cecr2 as a novel DNA damage response protein.

Keywords bromodomain, Cecr2, DNA damage response, gamma-H2AX, genome-wide screen

Article

Research Article

Mol. Cells 2012; 34(1): 85-91

Published online July 31, 2012 https://doi.org/10.1007/s10059-012-0112-4

Copyright © The Korean Society for Molecular and Cellular Biology.

Genome-Wide Screen of Human Bromodomain-Containing Proteins Identifies Cecr2 as a Novel DNA Damage Response Protein

Seul-Ki Lee1, Eun-Jung Park1, Han-Sae Lee, Ye Seul Lee, and Jongbum Kwon*

Department of Life Science, Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Korea, 1These authors contributed equally to this work.

Correspondence to:*Correspondence: jongkwon@ewha.ac.kr

Received: April 16, 2012; Accepted: May 2, 2012

Abstract

The formation of ?-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 ?-H2AX formation, and this function of BRG1 requires the binding of BRGI to acetylated histone H3 on ?-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 ?-H2AX and DSB repair. Here, we found that BRDs from a select group of proteins have no such activity, suggesting that the ?-H2AX inhibition activity of BRG1 BRD is specific. This finding led us to search for more BRDs that exhibit ?-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 ?-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 ?-H2AX formation and DSB repair. Therefore, our genome-wide screen identifies Cecr2 as a novel DNA damage response protein.

Keywords: bromodomain, Cecr2, DNA damage response, gamma-H2AX, genome-wide screen

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

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