2021
DOI: 10.1093/nar/gkab674
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Double-stranded flanking ends affect the folding kinetics and conformational equilibrium of G-quadruplexes forming sequences within the promoter of KIT oncogene

Abstract: G-quadruplexes embedded within promoters play a crucial role in regulating the gene expression. KIT is a widely studied oncogene, whose promoter contains three G-quadruplex forming sequences, c-kit1, c-kit2 and c-kit*. For these sequences available studies cover ensemble and single-molecule analyses, although for kit* the latter were limited to a study on a promoter domain comprising all of them. Recently, c-kit2 has been reported to fold according to a multi-step process involving folding intermediates. Here,… Show more

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Cited by 10 publications
(8 citation statements)
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“…Our model predictions of folding patterns are robust as long as K f, N -1 is greater than K f , and K f,N is significantly greater than K f, N -1 . The G-Tracts on the 5′ side (vicinity of ssDNA/dsDNA junction) are significantly less stable due to the flanking duplex regions, similar to a recent observation in KIT promoter ( 37 ). We estimated the folding parameters for these 5′ G-Tracts (K f,1 and K f,2 ) and the cooperativity parameter (K c ) by comparing the patterns observed for the experimentally measured and computationally calculated S-parameters, as described below.…”
Section: Resultssupporting
confidence: 81%
“…Our model predictions of folding patterns are robust as long as K f, N -1 is greater than K f , and K f,N is significantly greater than K f, N -1 . The G-Tracts on the 5′ side (vicinity of ssDNA/dsDNA junction) are significantly less stable due to the flanking duplex regions, similar to a recent observation in KIT promoter ( 37 ). We estimated the folding parameters for these 5′ G-Tracts (K f,1 and K f,2 ) and the cooperativity parameter (K c ) by comparing the patterns observed for the experimentally measured and computationally calculated S-parameters, as described below.…”
Section: Resultssupporting
confidence: 81%
“…On the 5′ side, our constructs have a ssDNA/dsDNA junction rather than a free end as in ssDNA, which resulted in significantly lower stability for G-Tracts in this region. A similar destabilization due to flanking duplex regions was recently reported for the GQs that form in KIT promoter (53). We estimated the folding parameters associated with the G-Tracts in the vicinity of ssDNA/dsDNA junction ( K f,1 and K f,2 ) and the cooperativity parameter ( K c ) by comparing the patterns observed for the experimentally measured and computationally calculated S-parameters, as described below.…”
Section: Resultssupporting
confidence: 81%
“…Properly designed single-molecule analyses can help to address this issue. In a recent study where FRET analyses were performed, a low sample concentration in solution prevented the occurrence of dimer formation [ 45 ]. As reported in Figure 3 b, two different constructs were designed.…”
Section: Differential Folding Landscapes Of G-quadruplexes At the ...mentioning
confidence: 99%