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 | |
| State | Published - Nov 2 2012 |
| Externally published | Yes |
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Keywords
- 53BP1
- DNA repair
- Ionizing radiation
- MacroH2A1
- Nucleosome
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
- Genetics
- Molecular Biology
- Structural Biology
Cite this
The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1. / Xu, Chang; Xu, Ye; Gursoy-Yuzugullu, Ozge; Price, Brendan D.
In: FEBS Letters, Vol. 586, No. 21, 02.11.2012, p. 3920-3925.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - The histone variant macroH2A1.1 is recruited to DSBs through a mechanism involving PARP1
AU - Xu, Chang
AU - Xu, Ye
AU - Gursoy-Yuzugullu, Ozge
AU - Price, Brendan D.
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
UR - http://www.scopus.com/inward/record.url?scp=84868093509&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84868093509&partnerID=8YFLogxK
U2 - 10.1016/j.febslet.2012.09.030
DO - 10.1016/j.febslet.2012.09.030
M3 - Article
C2 - 23031826
AN - SCOPUS:84868093509
VL - 586
SP - 3920
EP - 3925
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 21
ER -