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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2007.1
- 수록면
- 125 - 130 (6page)
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Purpose: Ataxia-telangiectasia mutated (ATM) kinase regulates diverse cellular DNA damage responses, including genome surveillance, cell growth, and gene expression. While the role of histone acetylation/deacetylation in gene expression is well established, little is known as to whether this modification can activate an ATM-dependent signal pathway, and whether this modification can thereby be implicated in an ATM-mediated DNA damage response.
Materials and Methods: Formation of H2AXγ foci was examined in HeLa and U2OS cells following treatment with a histone deacetylase inhibitor, Trichostatin A (TSA). We determine an ATM-dependency of the TSA-induced DNA damage signal pathway using isogenic A-T (ATM) and control (ATM+) cells. We monitored the phosphorylation of ATM, an ATM-downstream effector kinase, Chk2, and H2AXγ to detect the activation of the ATM-de pendent DNA damage signal pathway.
Results: Exposure of cells to TSA results in the formation of H2AXγ foci in HeLa and U2OS cells. The TSA-induced formation of H2AXγ foci occurs in an ATM-dependent manner. TSA induces phosphorylation of serine 1981 of ATM, accumulation of phosphorylated H2AX and Chk2, and formation of H2AX foci, in a manner analogous to genotoxic DNA damage.
Conclusion: In this work, we show that TSA induces a DNA damage signaling pathway in an ATM-dependent manner. These results suggest that ATM can respond to altered histone acetylation induced by the histone deacetylase inhibitor, TSA. (Cancer Res Treat. 2007;39:125- 130)
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참고문헌 (21)
참고문헌 신청
Bakkenist CJ / 2003 / DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation 421 : 499 ~ 506
Brush MH / 2004 / Deacetylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases 279 : 7685 ~ 7691
Burma S / 2001 / ATM phosphorylates histone H2AX in response to DNA double- strand breaks 276 : 42462 ~ 42467
Gatei M / 2000 / ATM-dependent phosphorylation of nibrin in response to radiation exposure 25 : 115 ~ 119
Gelmetti V / 1998 / Aberrant recruitment of the nuclear receptor corepressor- histone deacetylase complex by the acute myeloid leukemia fusion partner ETO 18 : 7185 ~ 7191
Brush MH / 2004 / Deacetylase inhibitors disrupt cellular complexes containing protein phosphatases and deacetylases 279 : 7685 ~ 7691
Burma S / 2001 / ATM phosphorylates histone H2AX in response to DNA double- strand breaks 276 : 42462 ~ 42467
Gatei M / 2000 / ATM-dependent phosphorylation of nibrin in response to radiation exposure 25 : 115 ~ 119
Gelmetti V / 1998 / Aberrant recruitment of the nuclear receptor corepressor- histone deacetylase complex by the acute myeloid leukemia fusion partner ETO 18 : 7185 ~ 7191
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