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| Status |
Public on Mar 15, 2010 |
| Title |
Altered levels of MOF and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR). |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Full title: Altered levels of MOF (member of MYST family histone acetyl transferase) and decreased levels of H4K16ac correlate with a defective DNA damage response (DDR).
The human MOF gene encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac). Here we show that altered levels of H4K16ac correlate with a defective DNA damage response (DDR) to ionizing radiation (IR). The defect however is not due to altered expression of proteins involved in DDR. Specific inhibition of H4K16ac deacetylation in MOF-depleted cells rescued IR-induced abrogation of DDR. MOF was found associated with DNA-dependent protein kinase catalytic subunit (DNAPKcs), a protein involved in non-homologous end joining (NHEJ) repair, whose ATMdependent IR-induced phosphorylation was abrogated in MOF-depleted cells. Our data indicate that MOF depletion greatly decreased the repair of DNA double-strand breaks (DSBs) by NHEJ and homologous recombination (HR). In addition, the MOF protein activity associates with chromatin upon DNA damage and colocalizes with the synaptonemal complex in male meiocytes. We propose that MOF, through H4K16ac, plays a critical role in the cellular DNA damage response.
Keywords: Cell type comparison
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| Overall design |
HEK293 cells were transfected with plasmids encoding hMOF for over-expression of the histone acetyl transferase that leads to elevated levels of acetylation of Lysine 16 of histone H4. siRNA mediated knock-down of hMOF was performed to deplete the H4K16ac levels. Total RNA samples for expression profiling was obtained from wild type (293 cells without any treatment), hMOF over-expressed and hMOF knock-down 293 cell lines. Each sample was analyzed in triplicates using EGPF dsRNA treated samples as control.
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| Contributor(s) |
Sharma G, Pandita T |
| Citation(s) |
20479123 |
| |
| Submission date |
Feb 04, 2010 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Rekha Meyer |
| E-mail(s) |
rmeyer@pathbox.wustl.edu
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| Phone |
314 362 8853
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| Organization name |
Washington University School of Medicine
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| Street address |
4320 Forest Park Av
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| City |
St Louis |
| State/province |
MO |
| ZIP/Postal code |
63128 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (9)
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| Relations |
| BioProject |
PRJNA125693 |
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