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Identification of Integrator-PP2A complex (INTAC), an RNA polymerase II phosphatase 期刊论文
Science, 2020
作者:  Hai Zheng;  Yilun Qi;  Shibin Hu;  Xuan Cao;  Congling Xu;  Zhinang Yin;  Xizi Chen;  Yan Li;  Weida Liu;  Jie Li;  Jiawei Wang;  Gang Wei;  Kaiwei Liang;  Fei Xavier Chen;  Yanhui Xu
收藏  |  浏览/下载:13/0  |  提交时间:2020/11/30
Oncometabolites suppress DNA repair by disrupting local chromatin signalling 期刊论文
NATURE, 2020
作者:  Zhang, Xu;  Lei, Bo;  Yuan, Yuan;  Zhang, Li;  Hu, Lu;  Jin, Sen;  Kang, Bilin;  Liao, Xuebin;  Sun, Wenzhi;  Xu, Fuqiang;  Zhong, Yi;  Hu, Ji;  Qi, Hai
收藏  |  浏览/下载:24/0  |  提交时间:2020/07/03

Metabolites that are elevated in tumours inhibit the lysine demethylase KDM4B, resulting in aberrant hypermethylation of histone 3 lysine 9 and decreased homology-dependent DNA repair.


Deregulation of metabolism and disruption of genome integrity are hallmarks of cancer(1). Increased levels of the metabolites 2-hydroxyglutarate, succinate and fumarate occur in human malignancies owing to somatic mutations in the isocitrate dehydrogenase-1 or -2 (IDH1 or IDH2) genes, or germline mutations in the fumarate hydratase (FH) and succinate dehydrogenase genes (SDHA, SDHB, SDHC and SDHD), respectively(2-4). Recent work has made an unexpected connection between these metabolites and DNA repair by showing that they suppress the pathway of homology-dependent repair (HDR)(5,6) and confer an exquisite sensitivity to inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials. However, the mechanism by which these oncometabolites inhibit HDR remains poorly understood. Here we determine the pathway by which these metabolites disrupt DNA repair. We show that oncometabolite-induced inhibition of the lysine demethylase KDM4B results in aberrant hypermethylation of histone 3 lysine 9 (H3K9) at loci surrounding DNA breaks, masking a local H3K9 trimethylation signal that is essential for the proper execution of HDR. Consequently, recruitment of TIP60 and ATM, two key proximal HDR factors, is substantially impaired at DNA breaks, with reduced end resection and diminished recruitment of downstream repair factors. These findings provide a mechanistic basis for oncometabolite-induced HDR suppression and may guide effective strategies to exploit these defects for therapeutic gain.


  
Hyperactivation of sympathetic nerves drives depletion of melanocyte stem cells 期刊论文
NATURE, 2020, 577 (7792) : 676-+
作者:  Zhao, Ruozhu;  Chen, Xin;  Ma, Weiwei;  Zhang, Jinyu;  Guo, Jie;  Zhong, Xiu;  Yao, Jiacheng;  Sun, Jiahui;  Rubinfien, Julian;  Zhou, Xuyu;  Wang, Jianbin;  Qi, Hai
收藏  |  浏览/下载:13/0  |  提交时间:2020/07/03

Empirical and anecdotal evidence has associated stress with accelerated hair greying (formation of unpigmented hairs)(1,2), but so far there has been little scientific validation of this link. Here we report that, in mice, acute stress leads to hair greying through the fast depletion of melanocyte stem cells. Using a combination of adrenalectomy, denervation, chemogenetics(3,4), cell ablation and knockout of the adrenergic receptor specifically in melanocyte stem cells, we find that the stress-induced loss of melanocyte stem cells is independent of immune attack or adrenal stress hormones. Instead, hair greying results from activation of the sympathetic nerves that innervate the melanocyte stem-cell niche. Under conditions of stress, the activation of these sympathetic nerves leads to burst release of the neurotransmitter noradrenaline (also known as norepinephrine). This causes quiescent melanocyte stem cells to proliferate rapidly, and is followed by their differentiation, migration and permanent depletion from the niche. Transient suppression of the proliferation of melanocyte stem cells prevents stress-induced hair greying. Our study demonstrates that neuronal activity that is induced by acute stress can drive a rapid and permanent loss of somatic stem cells, and illustrates an example in which the maintenance of somatic stem cells is directly influenced by the overall physiological state of the organism.


Stress induces hair greying in mice through depletion of melanocyte stem cells, which is mediated by the activation of sympathetic nerves rather than through immune attack or adrenal stress hormones.


  
Satellite testing of a gravitationally induced quantum decoherence model 期刊论文
SCIENCE, 2019, 366 (6461) : 132-+
作者:  Xu, Ping;  Ma, Yiqiu;  Ren, Ji-Gang;  Yong, Hai-Lin;  Ralph, Timothy C.;  Liao, Sheng-Kai;  Yin, Juan;  Liu, Wei-Yue;  Cai, Wen-Qi;  Han, Xuan;  Wu, Hui-Nan;  Wang, Wei-Yang;  Li, Feng-Zhi;  Yang, Meng;  Lin, Feng-Li;  Li, Li;  Liu, Nai-Le;  Chen, Yu-Ao;  Lu, Chao-Yang;  Chen, Yanbei;  Fan, Jingyun;  Peng, Cheng-Zhi;  Pan, Jian-Wei
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
Postcollisional delamination and partial melting of enriched lithospheric mantle: Evidence from Oligocene (ca. 30 Ma) potassium-rich lavas in the Gemuchaka area of the central Qiangtang Block, Tibet 期刊论文
GEOLOGICAL SOCIETY OF AMERICA BULLETIN, 2019, 131: 1385-1408
作者:  Ou, Quan;  Wang, Qiang;  Wyman, Derek A.;  Zhang, Chunfu;  Hao, Lu-Lu;  Dan, Wei;  Jiang, Zi-Qi;  Wu, Fu-Yuan;  Yang, Jin-Hui;  Zhang, Hai-Xiang;  Xia, Xiao-Ping;  Ma, Lin;  Long, Xiao-Ping;  Li, Jie
收藏  |  浏览/下载:15/0  |  提交时间:2019/11/27
牡蛎热休克蛋白70家族基因多样性和进化 项目
项目编号:41876169; 经费:620000(CNY); 起止日期:2019 / dc_date_end
项目负责人:  亓海刚
收藏  |  浏览/下载:6/0  |  提交时间:2019/11/27
The Remote Responses of Early Summer Cold Vortex Precipitation in Northeastern China to the precedent Sea Surface Temperatures 期刊论文
ATMOSPHERIC RESEARCH, 2018, 214: 399-409
作者:  Fang, Yi-He;  Chen, Kai-Qi;  Chen, Hai-Shan;  Xu, Shi-Qi;  Geng, Xin;  Li, Tian-Yu;  Teng, Fang-Da;  Zhou, Xiao-Yu;  Wang, Yong-Guang
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09
NEC  Early summer northeast cold vortex precipitation  Ural Mountains'  blocking high  Sea of Okhotsk'  s blocking high  Lake Baikal'  s blocking high  North Atlantic SST tripole  Kuroshio SST  Model sensitivity tests  
An autoimmune disease variant of IgG1 modulates B cell activation and differentiation 期刊论文
SCIENCE, 2018, 362 (6415) : 700-+
作者:  Chen, Xiangjun;  Sun, Xiaolin;  Yang, Wei;  Yang, Bing;  Zhao, Xiaozhen;  Chen, Shuting;  He, Lili;  Chen, Hui;  Yang, Changmei;  Xiao, Le;  Chang, Zai;  Guo, Jianping;  He, Jing;  Zhang, Fuping;  Zheng, Fang;  Hu, Zhibin;  Yang, Zhiyong;  Lou, Jizhong;  Zheng, Wenjie;  Qi, Hai;  Xu, Chenqi;  Zhang, Hong;  Shan, Hongying;  Zhou, Xu-jie;  Wang, Qingwen;  Shi, Yi;  Lai, Luhua;  Li, Zhanguo;  Liu, Wanli
收藏  |  浏览/下载:16/0  |  提交时间:2019/11/27
East Asian dust storm in May 2017: observations, modelling, and its influence on the Asia-Pacific region 期刊论文
ATMOSPHERIC CHEMISTRY AND PHYSICS, 2018, 18 (11) : 8353-8371
作者:  Zhang, Xiao-Xiao;  Sharratt, Brenton;  Liu, Lian-You;  Wang, Zi-Fa;  Pan, Xiao-Le;  Lei, Jia-Qiang;  Wu, Shi-Xin;  Huang, Shuang-Yan;  Guo, Yu-Hong;  Li, Jie;  Tang, Xiao;  Yang, Ting;  Tian, Yu;  Chen, Xue-Shun;  Hao, Jian-Qi;  Zheng, Hai-Tao;  Yang, Yan-Yan;  Lyu, Yan-Li
收藏  |  浏览/下载:15/0  |  提交时间:2019/04/09
Topographic Beta Spiral and Onshore Intrusion of the Kuroshio Current 期刊论文
GEOPHYSICAL RESEARCH LETTERS, 2018, 45 (1) : 287-296
作者:  Yang, De-Zhou;  Huang, Rui Xin;  Yin, Bao-shu;  Feng, Xing-Ru;  Chen, Hai-ying;  Qi, Ji-Feng;  Xu, Ling-jing;  Shi, Yun-long;  Cui, Xuan;  Gao, Guan-Dong;  Benthuysen, Jessica A.
收藏  |  浏览/下载:12/0  |  提交时间:2019/04/09