The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1

Chang Xu; Ye Xu; Ozge Gursoy-Yuzugullu; Brendan D. Price

doi:10.1016/j.febslet.2012.09.030

The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1

Chang Xu, Ye Xu, Ozge Gursoy-Yuzugullu, Brendan D. Price

Research output: Contribution to journal › Article › peer-review

53 Scopus citations

Abstract

The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage.

Original language	English (US)
Pages (from-to)	3920-3925
Number of pages	6
Journal	FEBS letters
Volume	586
Issue number	21
DOIs	https://doi.org/10.1016/j.febslet.2012.09.030
State	Published - Nov 2 2012
Externally published	Yes

Keywords

53BP1
DNA repair
Ionizing radiation
MacroH2A1
Nucleosome

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2012.09.030

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@article{ef8055a43d2f4f7f89e4dc894f39b396,

title = "The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1",

abstract = "The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage.",

keywords = "53BP1, DNA repair, Ionizing radiation, MacroH2A1, Nucleosome",

author = "Chang Xu and Ye Xu and Ozge Gursoy-Yuzugullu and Price, {Brendan D.}",

note = "Funding Information: We thank J. Stark for NHEJ reporter cells and B. Chadwick for mH2A1.1 and mH2A1.2 plasmids. Supported by Grants from the NCI (CA64585 and CA93602) to BDP. ",

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doi = "10.1016/j.febslet.2012.09.030",

language = "English (US)",

volume = "586",

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AU - Xu, Chang

AU - Xu, Ye

AU - Gursoy-Yuzugullu, Ozge

AU - Price, Brendan D.

N1 - Funding Information: We thank J. Stark for NHEJ reporter cells and B. Chadwick for mH2A1.1 and mH2A1.2 plasmids. Supported by Grants from the NCI (CA64585 and CA93602) to BDP.

PY - 2012/11/2

Y1 - 2012/11/2

N2 - The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage.

AB - The repair of DNA double-strand breaks (DSBs) requires remodeling of the local chromatin architecture to allow the repair machinery to access sites of damage. Here, we report that the histone variant macroH2A1.1 is recruited to DSBs. Cells lacking macroH2A1 have defective recruitment of 53BP1, defective activation of chk2 kinase and increased radiosensitivity. Importantly, macroH2A1.1 is not incorporated into nucleosomes at DSBs, but instead associates with the chromatin through a mechanism which requires PARP1 activity. These results reveal an unusual mechanism involving a direct association of macroH2A1.1 with PARylated chromatin which is critical for retaining 53BP1 at sites of damage.

KW - 53BP1

KW - DNA repair

KW - Ionizing radiation

KW - MacroH2A1

KW - Nucleosome

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ER -

The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1

Abstract

Keywords

ASJC Scopus subject areas

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