DNA损伤
衰老
细胞生物学
生物
端粒
转录因子
干扰素
干细胞
DNA修复
干扰素调节因子
信号转导
DNA
免疫学
遗传学
基因
作者
Qiujing Yu,Yuliya Katlinskaya,Christopher J. Carbone,Binghao Zhao,Kanstantsin V. Katlinski,Hui Zheng,Manti Guha,Ning Li,Qijun Chen,Ting Yang,Christopher J. Lengner,Roger A. Greenberg,F. Brad Johnson,Serge Y. Fuchs
出处
期刊:Cell Reports
[Elsevier]
日期:2015-05-01
卷期号:11 (5): 785-797
被引量:197
标识
DOI:10.1016/j.celrep.2015.03.069
摘要
Expression of type I interferons (IFNs) can be induced by DNA-damaging agents, but the mechanisms and significance of this regulation are not completely understood. We found that the transcription factor IRF3, activated in an ATM-IKKα/β-dependent manner, stimulates cell-autonomous IFN-β expression in response to double-stranded DNA breaks. Cells and tissues with accumulating DNA damage produce endogenous IFN-β and stimulate IFN signaling in vitro and in vivo. In turn, IFN acts to amplify DNA-damage responses, activate the p53 pathway, promote senescence, and inhibit stem cell function in response to telomere shortening. Inactivation of the IFN pathway abrogates the development of diverse progeric phenotypes and extends the lifespan of Terc knockout mice. These data identify DNA-damage-response-induced IFN signaling as a critical mechanism that links accumulating DNA damage with senescence and premature aging.
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