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KRAS原癌基因启动子区域内一个形成G-四链体序列的H、C和N化学位移归属

H, C, and N chemical shift assignments of a G-quadruplex forming sequence within the KRAS proto-oncogene promoter region.

作者信息

Marquevielle Julien, Kumar M V Vasantha, Mergny Jean-Louis, Salgado Gilmar F

机构信息

ARNA Laboratory, European Institute of Chemistry and Biology (IECB), Université de Bordeaux, Inserm U1212 - CNRS UMR 5320, 2, rue Robert Escarpit, 33607, Pessac, France.

出版信息

Biomol NMR Assign. 2018 Apr;12(1):123-127. doi: 10.1007/s12104-017-9793-0. Epub 2017 Nov 30.

Abstract

Single stranded guanine rich DNA (or RNA) sequences adopt noncanonical secondary structures called G-quadruplexes (G4). Functionally, quadruplexes control gene transcription and regulate activities such as replication, gene recombination or alternative splicing. Hence they are potential targets for cancer, neuronal, and viral related diseases. KRAS is one of the most mutated oncogenes in the genome of cancer cells and contains a nuclease hypersensitive element (NHE) sequence capable of forming G-quadruplexes via its six runs of guanines. In our work, we are interested in the NMR structure of the major G4 scaffold formed in the KRAS NHE region with a mutated sequence of 22 residues. Here, we report H, C and N chemical shift assignments the G4 formed within KRAS22RT sequence.

摘要

富含鸟嘌呤的单链DNA(或RNA)序列会形成一种称为G-四链体(G4)的非经典二级结构。在功能上,四链体控制基因转录并调节诸如复制、基因重组或可变剪接等活动。因此,它们是癌症、神经和病毒相关疾病的潜在靶点。KRAS是癌细胞基因组中最易发生突变的癌基因之一,其包含一个核酸酶超敏元件(NHE)序列,该序列能够通过其六组鸟嘌呤形成G-四链体。在我们的工作中,我们对KRAS NHE区域中形成的主要G4支架的NMR结构感兴趣,该区域具有一个22个残基的突变序列。在此,我们报告了KRAS22RT序列内形成的G4的H、C和N化学位移归属。

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