排序方式: 共有23条查询结果,搜索用时 15 毫秒
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Chang Yu Jun Yu Xiaotian Yao William KK Wu Youyong Lu Senwei Tang Xiangchun Li Li Bao Xiaoxing Li Yong Hou Renhua Wu Min Jian Ruoyan Chen Fan Zhang Lixia Xu Fan Fan Jun He Qiaoyi Liang Hongyi Wang Xueda Hu Minghui He Xiang Zhang Hancheng Zheng Qibin Li Hanjie Wu Yan Chen Xu Yang Shida Zhu Xun Xu Huanming Yang Jian Wang Xiuqing Zhang Joseph JY Sung Yingrui Li Jun Wang 《Cell research》2014,24(6):701-712
Single-cell sequencing is a powerful tool for delineating clonal relationship and identifying key driver genes for personalized cancer management. Here we performed single-cell sequencing analysis of a case of colon cancer. Population genetics analyses identified two independent clones in tumor cell population. The major tumor clone harbored APC and TP53 mutations as early oncogenic events, whereas the minor clone contained preponderant CDC27 and PABPC1 mutations. The absence of APC and TP53 mutations in the minor clone supports that these two clones were derived from two cellular origins. Examination of somatic mutation allele frequency spectra of additional 21 whole-tissue exome-sequenced cases revealed the heterogeneity of clonal origins in colon cancer. Next, we identified a mutated gene SLC12A5 that showed a high frequency of mutation at the single-cell level but exhibited low prevalence at the population level. Functional characterization of mutant SLC12A5 revealed its potential oncogenic effect in colon cancer. Our study provides the first exome-wide evidence at single-cell level supporting that colon cancer could be of a biclonal origin, and suggests that low-prevalence mutations in a cohort may also play important protumorigenic roles at the individual level. 相似文献
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Robin
z Jing L Wang Raphael Guerois Gaurav Goyal Sriram KK Virginie Ropars Rajhans Sharma Firat Koca Jean-Baptiste Charbonnier Mauro Modesti Terence R Strick Fredrik Westerlund 《Nucleic acids research》2021,49(5):2629
We use single-molecule techniques to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ), a system comprised only of the dimeric Ku and Ligase D (LigD). The Ku homodimer alone forms a ∼2 s synapsis between blunt DNA ends that is increased to ∼18 s upon addition of LigD, in a manner dependent on the C-terminal arms of Ku. The synapsis lifetime increases drastically for 4 nt complementary DNA overhangs, independently of the C-terminal arms of Ku. These observations are in contrast to human Ku, which is unable to bridge either of the two DNA substrates. We also demonstrate that bacterial Ku binds the DNA ends in a cooperative manner for synapsis initiation and remains stably bound at DNA junctions for several hours after ligation is completed, indicating that a system for removal of the proteins is active in vivo. Together these experiments shed light on the dynamics of bacterial NHEJ in DNA end recognition and processing. We speculate on the evolutionary similarities between bacterial and eukaryotic NHEJ and discuss how an increased understanding of bacterial NHEJ can open the door for future antibiotic therapies targeting this mechanism. 相似文献
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