Acetylation of H2AX on lysine 36 plays a key role in the DNA double-strand break repair pathway.
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.
Jiang
Xiaofeng
X
Division of Genomic Stability and DNA Repair, Department of Radiation Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Xu
Ye
Y
Price
Brendan D
BD
D000107:Acetylation; D015153:Blotting, Western; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair / Q000235:genetics / Q000502:physiology*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*
C468783:H2AX protein, human; D006657:Histones