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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 195 - 204 (10page)
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Chromatin structure has a crucial role in a diversity of physiological processes, including development, differentiation and stress responses, via regulation of transcription, DNA replication and DNA damage repair.
Histone deacetylase (HDAC) inhibitors regulate chromatin structure and activate the DNA damage checkpoint pathway involving Ataxia-telangiectasia mutated (ATM). Herein, we investigated the impact of histone acetylation/deacetylation modification on the ATM-mediated transcriptional modulation to provide a better understanding of the transcriptional function of ATM. The prototype HDAC inhibitor trichostain A (TSA) reprograms expression of the myeloid cell leukemia-1 (MCL1) and Gadd45α genes via the ATM-mediated signal pathway. Transcription of MCL1 and Gadd45α is enhanced following TSA treatment in ATM+cells, but not in isogenic ATM- or kinase-dead ATM expressing cells, in the ATM-activated E2F1 or BRCA1-dependent manner, respectively. These findings suggest that ATM and its kinase activity are essential for the TSA-induced regulation of gene expression. In summary, ATM controls the transcriptional upregulation of MCL1 and Gadd45α through the activation of the ATM-mediated signal pathway in response to HDAC inhibition. These findings are important in helping to design combinatory treatment schedules for anticancer radio- or chemo-therapy with HDAC inhibitors.
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참고문헌 (24)
참고문헌 신청
Akgul C / 2000 / Functional analysis of the human MCL1 gene / Cell Mol Life Sci 57 : 684 ~ 691
Attikum H van / 2009 / Crosstalk getween histone modifications during the DNA damage response / Trends in Cell Biol 19 : 207 ~ 217
Bakkenist CJ / 2003 / DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation / Nature 421 : 499 ~ 506
Criswell T / 2003 / Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation / Oncogene 22 : 5813 ~ 5827
Ferreiro JA / 2006 / Roles for Gen5p and Ada2p in transcription and nucleotide excision repair at the Saccharomyces cerevisiae Met16 gene / Nucleic Acid Res 34 : 976 ~ 985
Attikum H van / 2009 / Crosstalk getween histone modifications during the DNA damage response / Trends in Cell Biol 19 : 207 ~ 217
Bakkenist CJ / 2003 / DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation / Nature 421 : 499 ~ 506
Criswell T / 2003 / Transcription factors activated in mammalian cells after clinically relevant doses of ionizing radiation / Oncogene 22 : 5813 ~ 5827
Ferreiro JA / 2006 / Roles for Gen5p and Ada2p in transcription and nucleotide excision repair at the Saccharomyces cerevisiae Met16 gene / Nucleic Acid Res 34 : 976 ~ 985
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