DNA Secondary Structures: Stability and Function of G-quadruplex Structures

Overview

Journal Nat Rev Genet

Specialty Genetics

Date 2012 Oct 4

PMID 23032257

Citations 572

Authors

Matthew L Bochman

Katrin Paeschke

Virginia A Zakian

Affiliations

Soon will be listed here.

Abstract

In addition to the canonical double helix, DNA can fold into various other inter- and intramolecular secondary structures. Although many such structures were long thought to be in vitro artefacts, bioinformatics demonstrates that DNA sequences capable of forming these structures are conserved throughout evolution, suggesting the existence of non-B-form DNA in vivo. In addition, genes whose products promote formation or resolution of these structures are found in diverse organisms, and a growing body of work suggests that the resolution of DNA secondary structures is critical for genome integrity. This Review focuses on emerging evidence relating to the characteristics of G-quadruplex structures and the possible influence of such structures on genomic stability and cellular processes, such as transcription.

Citing Articles

Guanine Amine Derivatives Promote Forming a Base-Vacancy-G Quadruplex Structure.

Liang B, Zhu J, Yu H, Wu J, Ouyang F, Liu Y ACS Omega. 2025; 10(4):3820-3827.

PMID: 39926559 PMC: 11800147. DOI: 10.1021/acsomega.4c09242.

Position-Dependent Effects of AP Sites Within an Promoter G-Quadruplex Scaffold on Quadruplex Stability and Repair Activity of the APE1 Enzyme.

Savitskaya V, Novoselov K, Dolinnaya N, Monakhova M, Snyga V, Diatlova E Int J Mol Sci. 2025; 26(1.

PMID: 39796192 PMC: 11720163. DOI: 10.3390/ijms26010337.

Asymmetric distribution of G-quadruplex forming sequences in genomes of retroviruses.

Kledus F, Dobrovolna M, Mergny J, Brazda V Sci Rep. 2025; 15(1):76.

PMID: 39747944 PMC: 11696869. DOI: 10.1038/s41598-024-82613-2.

Copper(I)-Catalyzed Intramolecular Tandem Acylation/-Arylation under Mild Conditions: Synthesis of Benzofuro[3,2-]quinolin-6(5)-ones and G-Quadruplex-Targeting Analogues.

Chiou S, Lin Y, Chang Y, Chen Y, Lo T, Tsai C J Org Chem. 2024; 90(1):794-805.

PMID: 39726144 PMC: 11731314. DOI: 10.1021/acs.joc.4c02813.

Non-canonical DNA in human and other ape telomere-to-telomere genomes.

Smeds L, Kamali K, Kejnovska I, Kejnovsky E, Chiaromonte F, Makova K bioRxiv. 2024; .

PMID: 39713403 PMC: 11661062. DOI: 10.1101/2024.09.02.610891.

References

Sarkies P, Murat P, Phillips L, Patel K, Balasubramanian S, Sale J . FANCJ coordinates two pathways that maintain epigenetic stability at G-quadruplex DNA. Nucleic Acids Res. 2011; 40(4):1485-98. PMC: 3287192. DOI: 10.1093/nar/gkr868. View

Kim M, Vankayalapati H, Shin-Ya K, Wierzba K, Hurley L . Telomestatin, a potent telomerase inhibitor that interacts quite specifically with the human telomeric intramolecular g-quadruplex. J Am Chem Soc. 2002; 124(10):2098-9. DOI: 10.1021/ja017308q. View

Bugaut A, Balasubramanian S . 5'-UTR RNA G-quadruplexes: translation regulation and targeting. Nucleic Acids Res. 2012; 40(11):4727-41. PMC: 3367173. DOI: 10.1093/nar/gks068. View

Brown R, Danford F, Gokhale V, Hurley L, Brooks T . Demonstration that drug-targeted down-regulation of MYC in non-Hodgkins lymphoma is directly mediated through the promoter G-quadruplex. J Biol Chem. 2011; 286(47):41018-27. PMC: 3220475. DOI: 10.1074/jbc.M111.274720. View

Wang X, Haber J . Role of Saccharomyces single-stranded DNA-binding protein RPA in the strand invasion step of double-strand break repair. PLoS Biol. 2004; 2(1):E21. PMC: 314472. DOI: 10.1371/journal.pbio.0020021. View

Glickman B, Ripley L . Structural intermediates of deletion mutagenesis: a role for palindromic DNA. Proc Natl Acad Sci U S A. 1984; 81(2):512-6. PMC: 344708. DOI: 10.1073/pnas.81.2.512. View

Shklover J, Weisman-Shomer P, Yafe A, Fry M . Quadruplex structures of muscle gene promoter sequences enhance in vivo MyoD-dependent gene expression. Nucleic Acids Res. 2010; 38(7):2369-77. PMC: 2853122. DOI: 10.1093/nar/gkp1208. View

Hershman S, Chen Q, Lee J, Kozak M, Yue P, Wang L . Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae. Nucleic Acids Res. 2007; 36(1):144-56. PMC: 2248735. DOI: 10.1093/nar/gkm986. View

Pelengaris S, Khan M, Evan G . c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002; 2(10):764-76. DOI: 10.1038/nrc904. View

10.

Han H, Langley D, Rangan A, Hurley L . Selective interactions of cationic porphyrins with G-quadruplex structures. J Am Chem Soc. 2001; 123(37):8902-13. DOI: 10.1021/ja002179j. View

11.

Zaug A, Podell E, Cech T . Human POT1 disrupts telomeric G-quadruplexes allowing telomerase extension in vitro. Proc Natl Acad Sci U S A. 2005; 102(31):10864-9. PMC: 1180509. DOI: 10.1073/pnas.0504744102. View

12.

Fang G, Cech T . The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA. Cell. 1993; 74(5):875-85. DOI: 10.1016/0092-8674(93)90467-5. View

13.

Neidle S . The structures of quadruplex nucleic acids and their drug complexes. Curr Opin Struct Biol. 2009; 19(3):239-50. DOI: 10.1016/j.sbi.2009.04.001. View

14.

Brys A, Maizels N . LR1 regulates c-myc transcription in B-cell lymphomas. Proc Natl Acad Sci U S A. 1994; 91(11):4915-9. PMC: 43900. DOI: 10.1073/pnas.91.11.4915. View

15.

Simonsson T, Pecinka P, Kubista M . DNA tetraplex formation in the control region of c-myc. Nucleic Acids Res. 1998; 26(5):1167-72. PMC: 147388. DOI: 10.1093/nar/26.5.1167. View

16.

Boddupally P, Hahn S, Beman C, De B, Brooks T, Gokhale V . Anticancer activity and cellular repression of c-MYC by the G-quadruplex-stabilizing 11-piperazinylquindoline is not dependent on direct targeting of the G-quadruplex in the c-MYC promoter. J Med Chem. 2012; 55(13):6076-86. PMC: 3395776. DOI: 10.1021/jm300282c. View

17.

Lutz W, Leon J, Eilers M . Contributions of Myc to tumorigenesis. Biochim Biophys Acta. 2002; 1602(1):61-71. DOI: 10.1016/s0304-419x(02)00036-7. View

18.

Sun D, Hurley L . The importance of negative superhelicity in inducing the formation of G-quadruplex and i-motif structures in the c-Myc promoter: implications for drug targeting and control of gene expression. J Med Chem. 2009; 52(9):2863-74. PMC: 2757002. DOI: 10.1021/jm900055s. View

19.

Wyatt J, Davis P, Freier S . Kinetics of G-quartet-mediated tetramer formation. Biochemistry. 1996; 35(24):8002-8. DOI: 10.1021/bi960124h. View

20.

Sundquist W, Klug A . Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops. Nature. 1989; 342(6251):825-9. DOI: 10.1038/342825a0. View