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  • Unique structural features of G-quadruplexes from the intron of the N-myc gene [Elektronski vir]
    Plavec, Janez
    Guanine-rich DNA regions have been shown to fold into four stranded structures called G-quadruplexes. Possible biological roles of G-quadruplexes have been implicated in many vital cell mechanisms. ... The potential of G-quadruplexes as therapeutic targets has been well established with evidenceof their prevalence in telomeres and gene promoters. NMR has been successful in determining 3D structures of several unique architectures of G-quadruplexes consisting of stacked G-quartets each formed by assembly of four Hoogsteen hydrogen-bonded guanine residues. Stability of G-quadruplexes depends on a number of stacked G-quartets as well as on length and sequence details of loops that connect guanines involved in G-quartets. Orientations of the loops are tightly related to strand directionality of a G-quadruplex and give rise to high heterogeneity of G-quadruplex folding topologies. The Myc family comprises c-myc, N-myc and L-myc proto-oncogenes, which encode proteins involved in mechanisms regulating cell growth, differentiation, proliferation and apoptosis. Expression of N-myc gene is restricted to specifi tissues during their development. Its deregulation is associated with neuronal tumors. Amplificatio and level of expression of N-myc oncogene has been studied due to their connection with pathophysiology of neuroblastoma cancer. An NMR structural study on oligonucleotide d[TAG3CG3AG3AG3A2], originating from the firs intron of the N-myc gene, demonstrated formation of G-quadruplex in K+ ion containing solution. The monomeric form of the oligonucleotide comprises three G-quartets that are bridged with three single nucleotide propeller-type loops. The monomeric formis involved in equilibrium with a dimeric form. The topology of dimeric G-quadruplex is characterized by consecutive stacking of six G-quartets. The four strands adopt parallel orientations and are connected with propeller-type loops. A link between the third and the fourth G-quartets consists of two adenine residues that are flippe out to facilitate consecutive stacking of six G-quartets.
    Vir: 25th ICMRBS 2012 [Elektronski vir] (Str. 114)
    Vrsta gradiva - prispevek na konferenci
    Leto - 2012
    Jezik - angleški
    COBISS.SI-ID - 5049882

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