人类原癌基因c-kit内可能的DNA四链体形成。
Putative DNA quadruplex formation within the human c-kit oncogene.
作者信息
Rankin Sarah, Reszka Anthony P, Huppert Julian, Zloh Mire, Parkinson Gary N, Todd Alan K, Ladame Sylvain, Balasubramanian Shankar, Neidle Stephen
机构信息
Cancer Research UK Biomolecular Structure Group, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK.
出版信息
J Am Chem Soc. 2005 Aug 3;127(30):10584-9. doi: 10.1021/ja050823u.
Abstract
The DNA sequence, d(AGGGAGGGCGCTGGGAGGAGGG), occurs within the promoter region of the c-kit oncogene. We show here, using a combination of NMR, circular dichroism, and melting temperature measurements, that this sequence forms a four-stranded quadruplex structure under physiological conditions. Variations in the sequences that intervene between the guanine tracts have been examined, and surprisingly, none of these modified sequences forms a quadruplex arrangement under these conditions. This suggests that the occurrence of quadruplex-forming sequences within the human and other genomes is less than was hitherto expected. The c-kit quadruplex may be a new target for therapeutic intervention in cancers where there is elevated expression of the c-kit gene.
摘要
DNA序列d(AGGGAGGGCGCTGGGAGGAGGG)存在于原癌基因c-kit的启动子区域内。我们在此表明，通过结合核磁共振（NMR）、圆二色性和熔解温度测量，该序列在生理条件下形成四链体结构。已经研究了鸟嘌呤束之间插入序列的变化，令人惊讶的是，在这些条件下，这些修饰序列中没有一个形成四链体排列。这表明在人类和其他基因组中形成四链体的序列的出现频率低于迄今为止的预期。c-kit四链体可能是对c-kit基因表达升高的癌症进行治疗干预的新靶点。
相似文献
1
Putative DNA quadruplex formation within the human c-kit oncogene.人类原癌基因c-kit内可能的DNA四链体形成。
J Am Chem Soc. 2005 Aug 3;127(30):10584-9. doi: 10.1021/ja050823u.
2
A conserved quadruplex motif located in a transcription activation site of the human c-kit oncogene.位于人类c-kit癌基因转录激活位点的一个保守四链体基序。
Biochemistry. 2006 Jun 27;45(25):7854-60. doi: 10.1021/bi0601510.
3
Solution structures of all parallel-stranded monomeric and dimeric G-quadruplex scaffolds of the human c-kit2 promoter.人源 c-kit2 启动子所有平行股单链和双链 G-四链体支架的溶液结构。
Nucleic Acids Res. 2010 Oct;38(19):6757-73. doi: 10.1093/nar/gkq558. Epub 2010 Jun 21.
4
Polymorphism and resolution of oncogene promoter quadruplex-forming sequences.癌基因启动子四链体形成序列的多态性和分辨率。
Org Biomol Chem. 2011 Oct 26;9(22):7633-7. doi: 10.1039/c1ob05891f. Epub 2011 Sep 21.
5
Structure of an unprecedented G-quadruplex scaffold in the human c-kit promoter.人类c-kit启动子中一种前所未有的G-四链体支架结构。
J Am Chem Soc. 2007 Apr 11;129(14):4386-92. doi: 10.1021/ja068739h. Epub 2007 Mar 16.
6
A G-rich sequence within the c-kit oncogene promoter forms a parallel G-quadruplex having asymmetric G-tetrad dynamics.c-kit 癌基因启动子内的富含 G 序列形成具有不对称 G-四联体动力学的平行 G-四链体。
J Am Chem Soc. 2009 Sep 23;131(37):13399-409. doi: 10.1021/ja904007p.
7
A small molecule that disrupts G-quadruplex DNA structure and enhances gene expression.一种破坏G-四链体DNA结构并增强基因表达的小分子。
J Am Chem Soc. 2009 Sep 9;131(35):12628-33. doi: 10.1021/ja901892u.
8
An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution.在溶液中，人源BCL-2启动子区域形成了具有混合平行/反平行G链的分子内G-四链体结构。
J Am Chem Soc. 2006 Feb 1;128(4):1096-8. doi: 10.1021/ja055636a.
9
Sequence occurrence and structural uniqueness of a G-quadruplex in the human c-kit promoter.人类c-kit启动子中G-四链体的序列出现情况及结构独特性
Nucleic Acids Res. 2007;35(17):5799-808. doi: 10.1093/nar/gkm609. Epub 2007 Aug 24.
10
pH-Modulated Watson-Crick duplex-quadruplex equilibria of guanine-rich and cytosine-rich DNA sequences 140 base pairs upstream of the c-kit transcription initiation site.c-kit 转录起始位点上游 140 个碱基富含鸟嘌呤和胞嘧啶的 DNA 序列的 pH 调节的 Watson-Crick 双螺旋-四链体平衡。
Chemistry. 2009 Nov 23;15(46):12663-71. doi: 10.1002/chem.200901631.
引用本文的文献
1
DNA G-quadruplex profiling in skeletal muscle stem cells reveals functional and mechanistic insights.骨骼肌干细胞中的DNA G-四链体分析揭示了功能和机制方面的见解。
Genome Biol. 2025 Sep 5;26(1):269. doi: 10.1186/s13059-025-03753-w.
2
DNA G-Quadruplexes as Targets for Natural Product Drug Discovery.作为天然产物药物发现靶点的DNA G-四链体
Engineering (Beijing). 2024 Jul;38:39-51. doi: 10.1016/j.eng.2024.03.015. Epub 2024 May 6.
3
Phase Separation Oppositely Modulates G-quadruplex and i-Motif DNA Folding in the Nuclei of Living Cells.相分离对活细胞核中G-四链体和i-基序DNA折叠起相反的调节作用。
bioRxiv. 2025 Jul 4:2025.06.30.661982. doi: 10.1101/2025.06.30.661982.
4
APE1 promotes lung adenocarcinoma through G4-mediated transcriptional reprogramming of urea cycle metabolism.APE1通过G4介导的尿素循环代谢转录重编程促进肺腺癌。
iScience. 2025 Mar 25;28(5):112275. doi: 10.1016/j.isci.2025.112275. eCollection 2025 May 16.
5
Altering translation allows E. coli to overcome G-quadruplex stabilizers.改变翻译过程使大肠杆菌能够克服G-四链体稳定剂的影响。
Nucleic Acids Res. 2025 Mar 20;53(6). doi: 10.1093/nar/gkaf264.
6
Investigation of simple BODIPY dyes as G-quadruplex recognizing ligands.作为G-四链体识别配体的简单硼二吡咯类染料的研究。
RSC Adv. 2025 Feb 17;15(7):5220-5231. doi: 10.1039/d4ra08464k. eCollection 2025 Feb 13.
7
Effects of hydrazone-based G-quadruplex ligands on -depleted cancer cells and a strain.腙基G-四链体配体对 - 缺失癌细胞和一种菌株的影响。
需注意，原文中“-depleted”处似乎有信息缺失。
NAR Cancer. 2025 Feb 8;7(1):zcaf004. doi: 10.1093/narcan/zcaf004. eCollection 2025 Mar.
8
Kanamycin and G-Quadruplexes: An Exploration of Binding Interactions.卡那霉素与G-四链体：结合相互作用的探索
Molecules. 2024 Dec 16;29(24):5932. doi: 10.3390/molecules29245932.
9
Insights into the Molecular Structure, Stability, and Biological Significance of Non-Canonical DNA Forms, with a Focus on G-Quadruplexes and i-Motifs.非经典 DNA 结构、稳定性和生物学意义的分子结构研究进展，重点关注 G-四链体和 i- 型结构。
Molecules. 2024 Oct 2;29(19):4683. doi: 10.3390/molecules29194683.
10
The first embryonic landscape of G-quadruplexes related to myogenesis.与肌发生相关的第一个胚胎级联 G-四链体结构域。
BMC Biol. 2024 Sep 11;22(1):194. doi: 10.1186/s12915-024-01993-z.
本文引用的文献
1
Prevalence of quadruplexes in the human genome.人类基因组中四链体的患病率。
Nucleic Acids Res. 2005 May 24;33(9):2908-16. doi: 10.1093/nar/gki609. Print 2005.
2
Highly prevalent putative quadruplex sequence motifs in human DNA.人类DNA中高度普遍存在的假定四链体序列基序。
Nucleic Acids Res. 2005 May 24;33(9):2901-7. doi: 10.1093/nar/gki553. Print 2005.
3
Vertebrate telomere repeat DNAs favor external loop propeller quadruplex structures in the presence of high concentrations of potassium.在高浓度钾存在的情况下，脊椎动物端粒重复DNA倾向于形成外部环螺旋四重结构。
Nucleic Acids Res. 2005 Apr 7;33(6):2022-31. doi: 10.1093/nar/gki345. Print 2005.
4
Solution structure of the biologically relevant G-quadruplex element in the human c-MYC promoter. Implications for G-quadruplex stabilization.人类c-MYC启动子中生物学相关G-四链体元件的溶液结构。对G-四链体稳定化的影响。
Biochemistry. 2005 Feb 15;44(6):2048-58. doi: 10.1021/bi048242p.
5
c-kit expression in adenocarcinomas of the lung.c-kit在肺腺癌中的表达。
Tumour Biol. 2004 Sep-Dec;25(5-6):235-42. doi: 10.1159/000081386.
6
Loop-length-dependent folding of G-quadruplexes.G-四链体的环长度依赖性折叠
J Am Chem Soc. 2004 Dec 22;126(50):16405-15. doi: 10.1021/ja045154j.
7
Propeller-type parallel-stranded G-quadruplexes in the human c-myc promoter.人类c-myc启动子中的螺旋桨型平行链G-四链体
J Am Chem Soc. 2004 Jul 21;126(28):8710-6. doi: 10.1021/ja048805k.
8
The dynamic character of the G-quadruplex element in the c-MYC promoter and modification by TMPyP4.c-MYC启动子中G-四链体元件的动态特性及TMPyP4对其的修饰作用
J Am Chem Soc. 2004 Jul 21;126(28):8702-9. doi: 10.1021/ja040022b.
9
Two-repeat Tetrahymena telomeric d(TGGGGTTGGGGT) Sequence interconverts between asymmetric dimeric G-quadruplexes in solution.双重复四膜虫端粒 d(TGGGGTTGGGGT) 序列在溶液中于不对称二聚体 G-四链体之间相互转换。
J Mol Biol. 2004 Apr 16;338(1):93-102. doi: 10.1016/j.jmb.2004.02.042.
10
Targeting c-Kit mutations: basic science to novel therapies.靶向c-Kit突变：从基础科学到新型疗法
Leuk Res. 2004 May;28 Suppl 1:S11-20. doi: 10.1016/j.leukres.2003.10.004.
Zotero 插件