The catalytic properties of DNA G-quadruplexes rely on their structural integrity

doi:10.1016/S1872-2067(20)63744-5

Chinese Journal of Catalysis ›› 2021, Vol. 42 ›› Issue (7): 1102-1107.DOI: 10.1016/S1872-2067(20)63744-5

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The catalytic properties of DNA G-quadruplexes rely on their structural integrity

Jielin Chen^a,^†, Mingpan Cheng^a,^†, Jiawei Wang^a, Dehui Qiu^a, David Monchaud^b, Jean-Louis Mergny^a^,^c, Huangxian Ju^a^,^*(), Jun Zhou^a^,^#()

^aState Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, Jiangsu, China
^bInstitut de Chimie Moléculaire, Université de Bourgogne (ICMUB), CNRS UMR6302, UBFC Dijon 21000, France
^cLaboratoire d’Optique et Biosciences, Ecole Polytechnique, CNRS, INSERM, Institut Polytechnique de Paris, 91128 Palaiseau, France

Received:2020-10-10 Accepted:2020-11-11 Online:2021-07-18 Published:2020-12-10
Contact: Huangxian Ju,Jun Zhou
About author:^# E-mail: jun.zhou@nju.edu.cn
^* E-mail: hxju@nju.edu.cn;
First author contact:
^† These authors contributed equally to this work.
Supported by:
National Natural Science Foundation of China(21977045);National Natural Science Foundation of China(21635005);Fundamental Research Funds for the Central Universities(02051430210);Funds of Nanjing University(020514912216)

Abstract

Abstract:

The influence of the G-quartet structural integrity on the catalytic activity of the G-quadruplex (G4) was investigated by comparing the G4-DNAzyme performances of a series of G4s with a G-vacancy site and a G-triplex (G-tri). The results presented herein not only confirm that the structural integrity of the 3'-end G-quartet is necessary for G4s to be catalytically competent but also show how to remediate G-vacancy-mediated catalytic activity losses via the addition of guanine surrogates in an approach referred to as G-vacancy complementation strategy that is applicable to parallel G4s only. Furthermore, this study demonstrates that the terminal G-quartet could act as a proximal coordinating group and cooperate with the flanking nucleotide to activate the hemin cofactor.

Key words: G-quadruplex, G-quadruplex DNAzyme, G-vacancy, G-quartet integrity, Guanine surrogate

Jielin Chen, Mingpan Cheng, Jiawei Wang, Dehui Qiu, David Monchaud, Jean-Louis Mergny, Huangxian Ju, Jun Zhou. The catalytic properties of DNA G-quadruplexes rely on their structural integrity[J]. Chinese Journal of Catalysis, 2021, 42(7): 1102-1107.

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URL: https://www.cjcatal.com/EN/10.1016/S1872-2067(20)63744-5

https://www.cjcatal.com/EN/Y2021/V42/I7/1102

Figures/Tables 6

Table 1 DNA sequences used in this study.

Name	Sequences (5′-3′)
GV1	TT GTG T GGG T GGG T GGG T
GV2	TT GG T GGG T GGG T GGG T
GV2A	TT GG T GGG T GGG T GGG A
GV2TC	TT GG T GGG T GGG T GGG TC
PG4	TT GGG T GGG T GGG T GGG T
G4A	TT GGG T GGG T GGG T GGG A
G4TC	TT GGG T GGG T GGG T GGG TC
G-Tri	TT GGG T GGG T GGG
TG3T	T GGG T

Fig. 1. Schematic representation of the influence of the G-quartet integrity on the G4-DNAzyme activity. Upper panel: G4 with a G-vacancy site (GV) (structure of GV2 is shown here, PDB ID is 6K3X) can be completed by the free guanine surrogates [(acyclovir (A) and guanosine (G)]. Lower panel: the G-quartet integrity of a G-triplex (G-Tri) was restored with the single-stranded G-rich sequence TG3T.

Fig. 2. (a) G-vacancy complementation strategy with free guanine surrogates. G4-DNAzyme activity of (b) GVs and G4s, and (c) GV1, (d) GV2, (e) GV2A, and (f) GV2TC upon addition of increasing concentrations (2, 5, 20, 50, and 100 mol. equiv.) of guanine surrogates [acyclovir (A) and guanosine (G)].

Fig. 3. G4-DNAzyme activity of G-triplex (G-Tri) upon addition of increasing concentrations (5, 10, 20, and 50 mol equiv.) of TG3T.

Fig. 4. Catalytic performances of Holliday junction-constrained G4s: (a) Schematic representation of the seven different Holliday junction-induced G4 systems (HGV and HG4): with (HG4, HG4TC-1, and HG4TC-2) or without (HGV1, HGV1TC, HGV2, and HGV2TC) intact G-quartet, and some of them with flanking dTC (HGV1TC, HGV2TC, HG4TC-1, and HG4TC-2). (b) The G4-DNAzyme activity of GVs upon addition of increasing concentrations of acyclovir (A).

Fig. 5. Dissociation constants (Kd) between hemin and GVs (red bars), GVs upon addition of increasing concentrations of acyclovir (A) (green bars), and intact G4s (blue bars). Student’s t-tests were performed between intact G4s and GVs (containing GV2 integrated with acyclovir): *** means p < 0.001, i.e. the difference between each group data set is very significant.

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The catalytic properties of DNA G-quadruplexes rely on their structural integrity

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