Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway

Xiaofeng Jiang; Ye Xu; Brendan D. Price

doi:10.1016/j.febslet.2010.05.017

Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway

Xiaofeng Jiang, Ye Xu, Brendan D. Price

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

27 Scopus citations

Abstract

Phosphorylation of H2AX functions to recruit DNA repair complexes to sites of DNA damage. Here, we report that H2AX is constitutively acetylated on lysine 36 (H2AXK36Ac) by the CBP/p300 acetyltransferases. H2AXK36Ac is required for cells to survive exposure to ionizing radiation; however, H2AXK36Ac levels are not increased by DNA damage. Further, acetylation of H2AX did not affect phosphorylation of H2AX or the formation of DNA damage foci. Finally, cells with a double mutation in both the H2AX acetylation and phosphorylation sites were more radiosensitive than cells containing individual mutations. H2AXK36Ac is therefore a novel, constitutive histone modification located within the histone core region which regulates radiation sensitivity independently of H2AX phosphorylation.

Original language	English (US)
Pages (from-to)	2926-2930
Number of pages	5
Journal	FEBS letters
Volume	584
Issue number	13
DOIs	https://doi.org/10.1016/j.febslet.2010.05.017
State	Published - Jul 2010
Externally published	Yes

Keywords

Acetylation
Chromatin
DNA double-strand break
H2AX
Histone acetyltransferase
IR

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2010.05.017

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@article{406fd588c43546e29fc788e9d199e126,

title = "Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway",

abstract = "Phosphorylation of H2AX functions to recruit DNA repair complexes to sites of DNA damage. Here, we report that H2AX is constitutively acetylated on lysine 36 (H2AXK36Ac) by the CBP/p300 acetyltransferases. H2AXK36Ac is required for cells to survive exposure to ionizing radiation; however, H2AXK36Ac levels are not increased by DNA damage. Further, acetylation of H2AX did not affect phosphorylation of H2AX or the formation of DNA damage foci. Finally, cells with a double mutation in both the H2AX acetylation and phosphorylation sites were more radiosensitive than cells containing individual mutations. H2AXK36Ac is therefore a novel, constitutive histone modification located within the histone core region which regulates radiation sensitivity independently of H2AX phosphorylation.",

keywords = "Acetylation, Chromatin, DNA double-strand break, H2AX, Histone acetyltransferase, IR",

author = "Xiaofeng Jiang and Ye Xu and Price, {Brendan D.}",

note = "Funding Information: We thank members of the Price laboratory, Anyong Xie and Ralph Scully for valuable discussions and sharing unpublished data; X. Yang and Q. Liu for providing HAT constructs; J. Chen for MDC1 antibody and A. Nussenzweig for H2AX −/− MEF cells. Supported by grants from the NCI ( CA64585 and CA93602 ) and the DOD Breast Cancer Program to BDP.",

year = "2010",

month = jul,

doi = "10.1016/j.febslet.2010.05.017",

language = "English (US)",

volume = "584",

pages = "2926--2930",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "Elsevier",

number = "13",

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T1 - Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway

AU - Jiang, Xiaofeng

AU - Xu, Ye

AU - Price, Brendan D.

N1 - Funding Information: We thank members of the Price laboratory, Anyong Xie and Ralph Scully for valuable discussions and sharing unpublished data; X. Yang and Q. Liu for providing HAT constructs; J. Chen for MDC1 antibody and A. Nussenzweig for H2AX −/− MEF cells. Supported by grants from the NCI ( CA64585 and CA93602 ) and the DOD Breast Cancer Program to BDP.

PY - 2010/7

Y1 - 2010/7

N2 - Phosphorylation of H2AX functions to recruit DNA repair complexes to sites of DNA damage. Here, we report that H2AX is constitutively acetylated on lysine 36 (H2AXK36Ac) by the CBP/p300 acetyltransferases. H2AXK36Ac is required for cells to survive exposure to ionizing radiation; however, H2AXK36Ac levels are not increased by DNA damage. Further, acetylation of H2AX did not affect phosphorylation of H2AX or the formation of DNA damage foci. Finally, cells with a double mutation in both the H2AX acetylation and phosphorylation sites were more radiosensitive than cells containing individual mutations. H2AXK36Ac is therefore a novel, constitutive histone modification located within the histone core region which regulates radiation sensitivity independently of H2AX phosphorylation.

AB - Phosphorylation of H2AX functions to recruit DNA repair complexes to sites of DNA damage. Here, we report that H2AX is constitutively acetylated on lysine 36 (H2AXK36Ac) by the CBP/p300 acetyltransferases. H2AXK36Ac is required for cells to survive exposure to ionizing radiation; however, H2AXK36Ac levels are not increased by DNA damage. Further, acetylation of H2AX did not affect phosphorylation of H2AX or the formation of DNA damage foci. Finally, cells with a double mutation in both the H2AX acetylation and phosphorylation sites were more radiosensitive than cells containing individual mutations. H2AXK36Ac is therefore a novel, constitutive histone modification located within the histone core region which regulates radiation sensitivity independently of H2AX phosphorylation.

KW - Acetylation

KW - Chromatin

KW - DNA double-strand break

KW - H2AX

KW - Histone acetyltransferase

KW - IR

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SN - 0014-5793

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ER -

Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway

Abstract

Keywords

ASJC Scopus subject areas

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