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G-quadruplex forming sequences are prevalent in eukaryotic cells, especially in telomeres, 5` untranslated strands, and translocation hot spots. G-quadruplexes can inhibit normal cell function, and in healthy cells, are easily and readily unwound by helicase. However, in cancer cells that have mutated helicase these complexes cannot be unwound ...
[1] [2] They most prominently contribute to the structure of G-quadruplexes, where their hydrogen bonding stabilizes the structure. [3] [4] Usually, there are at least two guanine tetrads in a G-quadruplex, and they often feature Hoogsteen-style hydrogen bonding. [1] Guanine tetrads are formed by sequences rich in guanine, such as GGGGC. [5]
These secondary structures possess guanine tetrads formed into one of three types of strands: one, two, or four. With prior knowledge of G-quadruplex forming sequences being susceptible to i-motif DNA formation, Waller's group used the algorithm Quadparser to determine the amount of i-motif forming sequences in the human genome. [22]
The nucleotides 1-3 and 25-27 with an additional C4-G23 form a duplex motif, and the sequence ranging from G5 to G20 folds into a G-quadruplex structure with four connection loops: T9-A10, T18-T19, G13-C14-A15 and a one-nucleotide loop (T6). In the core of G-quadruplex motif, two G-tetrad planes are formed by G5-G7-G12-G16 and G8-G11-G17-G20.
The G-quartet typically binds monovalent cations such as potassium, while other bases can bind numerous other ligands such as hypoxanthine in a U-U-C-U quadruplex. [17] Along with these functions, the G-quadruplex in the mRNA around the ribosome binding regions could serve as a regulator of gene expression in bacteria. [19]
Hoogsteen pointed out that if the alternative hydrogen-bonding patterns were present in DNA, then the double helix would have to assume a quite different shape. Hoogsteen base pairs are observed in alternative structures such as the four-stranded G-quadruplex structures that form in DNA and RNA.
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It is possible that these sequence stretches form G-quadruplex like structures, which can suppress the expression of the related genes. The complementary cytosine rich sequences, on the other strand, may adopt another similar four stranded structure, the i-motif, stabilized by cytosine:cytosine non-canonical base pairs.