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首页> 外文期刊>Biochemistry >Thermodynamic Stability and Folding Kinetics of the Major G-Quadruplex and Its Loop Isomers Formed in the Nuclease Hypersensitive Element in the Human c-Myc Promoter: Effect of Loops and Flanking Segments on the Stability of Parallel-Stranded Intramolecular G-Quadruplexes
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Thermodynamic Stability and Folding Kinetics of the Major G-Quadruplex and Its Loop Isomers Formed in the Nuclease Hypersensitive Element in the Human c-Myc Promoter: Effect of Loops and Flanking Segments on the Stability of Parallel-Stranded Intramolecular G-Quadruplexes

机译：人类c-Myc启动子中主要的G四联体及其核酸酶超敏元件中形成的环异构体的热力学稳定性和折叠动力学：环和侧翼节对平行链内分子G四联体稳定性的影响。

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Overexpression of the c-Myc proto-oncogene is associated with a broad spectrum of humanncancers. Nuclease hypersensitivity element III1 (NHE III1) of the c-Myc promoter can form transcriptionallynactive and silenced forms, and the formation of DNA G-quadruplex structures has been shown to be criticalnfor c-Myc transcriptional silencing. The major G-quadruplex formed in c-Myc NHE III1 is a mixture of fournloop isomers, which have all been shown to be biologically relevant to c-Myc transcriptional control. In thisnstudy, we performed a thorough thermodynamic and kinetic study of the four c-Myc loop isomers in a Kþnsolution. The four loop isomers all form parallel-stranded G-quadruplexes with short loop lengths.While thenparallel-stranded G-quadruplex has been known to favor short loop lengths, our results show that thendifference in thermodynamic and kinetic properties of the four loop isomers, and hence between the parallelnG-quadruplexes with similar loop lengths, is more significant than previously recognized. At 20 mMKþ, thenaverage difference in the Tm values between themost stable loop isomer 14/23 and the least stable loop isomern11/20 is more than 10 u0001C. In addition, the capping structures formed by the extended flanking segments arenshown to contribute to a stabilization of 2-3 u0001Cin Tm for the c-Myc promoterG-quadruplex.Understandingnthe intrinsic thermodynamic stability and kinetic properties of the c-Myc G-quadruplex loop isomers can aidnin our understanding of their biological roles and drug targeting.
机译：c-Myc原癌基因的过表达与广泛的人类癌症有关。 c-Myc启动子的核酸酶超敏元件III1（NHE III1）可以形成转录无活性和沉默形式，DNA G-四链体结构的形成已证明对c-Myc转录沉默至关重要。在c-Myc NHE III1中形成的主要G-四链体是Fournloop异构体的混合物，所有这些都已显示出与c-Myc转录控制生物学相关。在本研究中，我们对Knnsolution中的四个c-Myc环异构体进行了彻底的热力学和动力学研究。四个环异构体均形成短环长度的平行链G-四链体，虽然众所周知，然后平行链G-四链体倾向于短环长度，但我们的结果表明，四个环异构体的热力学和动力学性质存在差异。因此，在具有相似环路长度的平行G四联体之间比以前认识到的更为重要。在20mMK 4时，最稳定的环状异构体14/23和最不稳定的环状异构体11/20之间的Tm值的平均差大于10u0001C。此外，未显示由延伸的侧翼片段形成的封端结构有助于c-Myc启动子G-四链体稳定2-3 u0001Cin Tm.c-Myc G-四链体环异构体的固有热力学稳定性和动力学性质。可以帮助我们了解其生物学作用和靶向药物。

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    《Biochemistry》 |2010年第43期|p.9152-9160|共9页
  • 作者

    Emmanuel Hatzakis Keika Okamoto and Danzhou Yang;

  • 作者单位

    College of Pharmacy, The University of Arizona, 1703 East Mabel Street, Tucson, Arizona 85721, United States, and§BIO5 Institute, The University of Arizona, Tucson, Arizona 85721, United States, Arizona Cancer Center, 1515 North CampbellAvenue, Tucson, Arizona 85721, United States, and Department of Chemistry, The University of Arizona, Tucson,Arizona 85721, United States;

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