SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons
文献类型：期刊论文
| 作者 | Dobbin, Matthew M.2,3,4; Madabhushi, Ram2,3,4; Pan, Ling2,3,4; Chen, Yue1,5; Kim, Dohoon6; Gao, Jun2,3,4; Ahanonu, Biafra2,3,4; Pao, Ping-Chieh2,3,4; Qiu, Yi7; Zhao, Yingming1,5
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| 刊名 | NATURE NEUROSCIENCE
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| 出版日期 | 2013-08 |
| 卷号 | 16期号:8页码:1008-U54 |
| ISSN号 | 1097-6256 |
| DOI | 10.1038/nn.3460 |
| 文献子类 | Article |
| 英文摘要 | Defects in DNA repair have been linked to cognitive decline with age and neurodegenerative disease, yet the mechanisms that protect neurons from genotoxic stress remain largely obscure. We sought to characterize the roles of the NAD+-dependent deacetylase SIRT1 in the neuronal response to DNA double-strand breaks (DSBs). We found that SIRT1 was rapidly recruited to DSBs in postmitotic neurons, where it showed a synergistic relationship with ataxia telangiectasia mutated (ATM). SIRT1 recruitment to breaks was ATM dependent; however, SIRT1 also stimulated ATM autophosphorylation and activity and stabilized ATM at DSB sites. After DSB induction, SIRT1 also bound the neuroprotective class I histone deacetylase HDAC1. We found that SIRT1 deacetylated HDAC1 and stimulated its enzymatic activity, which was necessary for DSB repair through the nonhomologous end-joining pathway. HDAC1 mutations that mimic a constitutively acetylated state rendered neurons more susceptible to DNA damage, whereas pharmacological SIRT1 activators that promoted HDAC1 deacetylation also reduced DNA damage in two mouse models of neurodegeneration. We propose that SIRT1 is an apical transducer of the DSB response and that SIRT1 activation offers an important therapeutic avenue in neurodegeneration. |
| WOS关键词 | AMYOTROPHIC-LATERAL-SCLEROSIS ; DOUBLE-STRAND BREAKS ; DNA-DAMAGE ; CHROMATIN IMMUNOPRECIPITATION ; ALZHEIMERS-DISEASE ; CROSS-LINKING ; I-TASSER ; PROTEIN ; ACTIVATION ; ACETYLATION |
| 资助项目 | US National Institutes of Health (NIH)[AG27916] ; Howard Hughes Medical Institute[00000000] ; Neurodegeneration Consortium[00000000] ; Glenn award for research in biological mechanisms of aging[00000000] ; NIH[R01 HL095674] ; NIH[U54 RR020389] ; NIH[T32 GM007484] ; NIH[T32 MH081728] |
| WOS研究方向 | Neurosciences & Neurology |
| 语种 | 英语 |
| WOS记录号 | WOS:000322323000010 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277524]  |
| 专题 | 化学蛋白质组学研究中心 |
| 通讯作者 | Tsai, Li-Huei |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 200031, Peoples R China; 2.MIT, Picower Inst Learning & Memory, Cambridge, MA 02139 USA; 3.MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA; 4.MIT, Howard Hughes Med Inst, Cambridge, MA 02139 USA; 5.Univ Chicago, Ben May Dept Canc Res, Chicago, IL 60637 USA; 6.Whitehead Inst Biomed Res, Cambridge, MA 02142 USA; 7.Univ Florida, Dept Anat & Cell Biol, Gainesville, FL USA |
| 推荐引用方式 GB/T 7714 | Dobbin, Matthew M.,Madabhushi, Ram,Pan, Ling,et al. SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons[J]. NATURE NEUROSCIENCE,2013,16(8):1008-U54. |
| APA | Dobbin, Matthew M..,Madabhushi, Ram.,Pan, Ling.,Chen, Yue.,Kim, Dohoon.,...&Tsai, Li-Huei.(2013).SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons.NATURE NEUROSCIENCE,16(8),1008-U54. |
| MLA | Dobbin, Matthew M.,et al."SIRT1 collaborates with ATM and HDAC1 to maintain genomic stability in neurons".NATURE NEUROSCIENCE 16.8(2013):1008-U54. |
入库方式： OAI收割
来源：上海药物研究所
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