UV Melting of G‐Quadruplexes

Mergny, Jean‐Louis; Lacroix, Laurent

doi:10.1002/0471142700.nc1701s37

Cited by 169 publications

(185 citation statements)

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“…The melting temperature (T m ) values and other thermodynamic parameters were calculated using the Van't Hoff method. 75 RNase T1 footprinting. RNA oligonucleotides were 5'-endlabeled with 32 P, as previously described, 76 and pre-folded, as described above.…”

Section: Methodsmentioning

confidence: 99%

Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

et al. 2012

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cyclin D3 (CCND3) is one of the three D-type cyclins that regulate the G1/S phase transition of the cell cycle. Expression of CCND3 is observed in nearly all proliferating cells; however, the presence of high levels of CCND3 has been linked to a poor prognosis for several types of cancer. Therefore, further mechanistic studies on the regulation of CCND3 expression are urgently needed to provide therapeutic implications. In this study, we report that a conserved RNA G-quadruplex-forming sequence (hereafter CRQ), located in the 5' UTR of mammalian CCND3 mRNA, is able to fold into an extremely stable, intramolecular, parallel G-quadruplex in vitro. The CRQ G-quadruplex dramatically reduces the activity of a reporter gene in human cell lines, but it has little impact on its mRNA level, indicating a translational repression. Moreover, the CRQ sequence in its natural context inhibits translation of CCND3. Disruption of the G-quadruplex structure by G/U-mutation or deletion results in an elevated expression of CCND3 and an increased phosphorylation of Rb, a downstream target of CCND3, which promotes progression of cells through the G1 phase. Our results add to the growing understanding of the regulation of CCND3 expression and provide a potential therapeutic target for cancer treatment.

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Section: Methodsmentioning

confidence: 99%

Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

et al. 2012

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“…This result implies that the Cu 2+ ion has little or no destabilizing effect on the G-quadruplex structure in ODN-1-Cu 2+ . [13] UV Resonance Raman spectroscopy was used to further confirm the G4DNA structure. When ODN-1 interacts with the Cu 2+ ion, the three characteristic Raman bands (1484, 1580, and 1605 cm À1 ) are retained and the intensity of the two spectra is almost identical (Figure S4 c), implying that the Hoogsteen hydrogen bonds and base-stacking interactions are not significantly affected.…”

Section: +mentioning

confidence: 99%

Enantioselective Diels–Alder Reactions with G‐Quadruplex DNA‐Based Catalysts

et al. 2012

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Deoxyribonucleic acid (DNA) is the genetic material of living organisms. In the past, double-stranded DNA (dsDNA) with its ubiquitous architecture has not been regarded as a catalytic species, since the duplex structure precludes the formation of catalytically competent tertiary structures.[1] To date, although no naturally occurring catalytic DNA has been reported, DNA for nonbiological applications has aroused much interest in chemists for applications in areas such as catalysis, encoding, and stereocontrol.[2] Among these applications, a series of DNA-based asymmetric catalysis have been developed, which use a hybrid catalyst composed of dsDNA and a copper(II) complex.[3] This same strategy was later applied to G-quadruplex DNA (G4DNA) and modest enantioselectivities in the Diels-Alder (D-A) reaction were obtained.[4] Very recently, a G4DNA metalloenzyme composed of G4DNA and copper(II) ions has been reported to be able to catalyze an enantioselective Friedel-Crafts reaction. [5] This biology/chemistry interface is an attractive area of research and awaits further extensive exploration. Herein, we report an enantioselective D-A reaction achieved through the use of human telomeric G4DNA-based catalysts. We show that the absolute configuration of the products can be reversed when the conformation of the G4DNA is switched from antiparallel to parallel. Furthermore, both the reaction rate and the enantioselectivity of the reaction were found to be dependent on the DNA sequence.The D-A reaction is an important carbon-carbon bond forming reaction in organic synthesis. In the past few decades, it has received much attention in the development of innovative catalytic strategies to control the creation of the new carbon-carbon bonds and stereocenters. Among those strategies, biological molecules have been viewed as interesting and promising catalysts.[6] Herein, human telomeric G4DNA (ODN-1, 5'-G 3 (T 2 AG 3 ) 3 -3') was selected owing to its tunable conformation. As an initial attempt, a model D-A reaction [7] between aza-chalcone (1 a) and cyclopentadiene (2) was chosen to probe the catalytic performance of ODN-1. We found that ODN-1 alone in its antiparallel conformation [8] could promote the D-A reaction and the enantiomeric excess of the endo isomer of product 3 a is 17 % (Table 1, entry 2).The enantioselectivity of the ODN-1 promoted D-A reaction is significantly higher than that of the uncatalyzed reaction (Table 1, entry 2 vs. entry 1), which suggests that ODN-1 might function as an enantioselective catalyst for the D-A reaction.We assembled a complex between Cu(NO 3 ) 2 and ODN-1 (ODN-1-Cu 2+ ) and tested its ability to enantioselectively catalyze the D-A reaction. ODN-1-Cu 2+ provides a significant enhancement in the reaction rate ( entry 3). We also observed an excellent diastereoselectivity for product 3 a (endo/exo of 98:2) and a good enantioselectivity (74 % ee). These results suggest that ODN-1-Cu 2+ can serve as a potent catalyst, providing stereoselectivity and enhancement in reaction rates. To furthe...

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“…A detailed protocol for UV melting studies of quadruplexes was prepared by J.L. Mergny and L. Lacroix (2009).…”

Section: Uv Spectroscopymentioning

confidence: 99%

How to study G-quadruplex structures

Małgowska¹,

Gudanis²,

Teubert³

et al. 2012

bta

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All guanine-rich DNA and RNA molecules tend to fold into inter-and intra-molecular structures called G-quadruplexes. The core of a G-quadruplex is composed of at least two adjacent G-tetrads stabilized by monovalent cations. While it has been suggested that there could potentially be over 375 000 quadruplex forming sequences in the human genome alone, only a small number of three-dimensional G-quadruplex structures are known. More structural data are needed to explain their presence and function in vivo. We offer here a short review of experimental methods commonly used to determine G-quadruplex topologies.

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UV Melting of G‐Quadruplexes

Cited by 169 publications

References 25 publications

Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

Translational repression of cyclin D3 by a stable G-quadruplex in its 5′ UTR: implications for cell cycle regulation

Enantioselective Diels–Alder Reactions with G‐Quadruplex DNA‐Based Catalysts

How to study G-quadruplex structures

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