DNA G-quadruplexes in the Human Genome: Detection, Functions and Therapeutic Potential

Overview

Journal Nat Rev Mol Cell Biol

Specialties Cell Biology
Molecular Biology

Date 2017 Feb 23

PMID 28225080

Citations 326

Authors

Robert Hansel-Hertsch

Marco Di Antonio

Shankar Balasubramanian

Affiliations

Soon will be listed here.

Abstract

Single-stranded guanine-rich DNA sequences can fold into four-stranded DNA structures called G-quadruplexes (G4s) that arise from the self-stacking of two or more guanine quartets. There has been considerable recent progress in the detection and mapping of G4 structures in the human genome and in biologically relevant contexts. These advancements, many of which align with predictions made previously in computational studies, provide important new insights into the functions of G4 structures in, for example, the regulation of transcription and genome stability, and uncover their potential relevance for cancer therapy.

Citing Articles

G-Quadruplex Structures Formed by Human Telomere and GGGGCC Repeats.

Yan B, Suen M, Xu N, Lu C, Liu C, Zhu G Int J Mol Sci. 2025; 26(4).

PMID: 40004056 PMC: 11855686. DOI: 10.3390/ijms26041591.

Combining CRISPR activation and interference capabilities using dCas9 and G-quadruplex structures.

Kabir M, Kodikara S, Hoque M, Shiekh S, Alfehaid J, Basu S NAR Mol Med. 2025; 2(1):ugaf001.

PMID: 39906285 PMC: 11788920. DOI: 10.1093/narmme/ugaf001.

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.

Oligostyrylbenzene Derivatives with Antiparasitic and Antibacterial Activity as Potent G-Quadruplex Ligands.

Perez-Soto M, Penalver P, Munoz-Baez P, Tolosa J, Garcia-Martinez J, Cebrian R Molecules. 2025; 29(24.

PMID: 39769964 PMC: 11679705. DOI: 10.3390/molecules29245875.

Metallo-supramolecular complexes enantioselectively target monkeypox virus RNA G-quadruplex and bolster immune responses against MPXV.

Yang J, Qin G, Huang B, Song H, Sun J, Postings M Natl Sci Rev. 2025; 12(1):nwae388.

PMID: 39758126 PMC: 11697978. DOI: 10.1093/nsr/nwae388.

References

Nguyen G, Tang W, Robles A, Beyer R, Gray L, Welsh J . Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs. Proc Natl Acad Sci U S A. 2014; 111(27):9905-10. PMC: 4103369. DOI: 10.1073/pnas.1404807111. View

Zahler A, Williamson J, Cech T, Prescott D . Inhibition of telomerase by G-quartet DNA structures. Nature. 1991; 350(6320):718-20. DOI: 10.1038/350718a0. View

Henderson A, Wu Y, Huang Y, Chavez E, Platt J, Johnson F . Detection of G-quadruplex DNA in mammalian cells. Nucleic Acids Res. 2013; 42(2):860-9. PMC: 3902944. DOI: 10.1093/nar/gkt957. View

Bochman M, Paeschke K, Zakian V . DNA secondary structures: stability and function of G-quadruplex structures. Nat Rev Genet. 2012; 13(11):770-80. PMC: 3725559. DOI: 10.1038/nrg3296. View

Paeschke K, Juranek S, Simonsson T, Hempel A, Rhodes D, Lipps H . Telomerase recruitment by the telomere end binding protein-beta facilitates G-quadruplex DNA unfolding in ciliates. Nat Struct Mol Biol. 2008; 15(6):598-604. DOI: 10.1038/nsmb.1422. View

Gray L, Vallur A, Eddy J, Maizels N . G quadruplexes are genomewide targets of transcriptional helicases XPB and XPD. Nat Chem Biol. 2014; 10(4):313-8. PMC: 4006364. DOI: 10.1038/nchembio.1475. View

Piazza A, Boule J, Lopes J, Mingo K, Largy E, Teulade-Fichou M . Genetic instability triggered by G-quadruplex interacting Phen-DC compounds in Saccharomyces cerevisiae. Nucleic Acids Res. 2010; 38(13):4337-48. PMC: 2910037. DOI: 10.1093/nar/gkq136. View

Besnard E, Babled A, Lapasset L, Milhavet O, Parrinello H, Dantec C . Unraveling cell type-specific and reprogrammable human replication origin signatures associated with G-quadruplex consensus motifs. Nat Struct Mol Biol. 2012; 19(8):837-44. DOI: 10.1038/nsmb.2339. View

David A, Margarit E, Domizi P, Banchio C, Armas P, Calcaterra N . G-quadruplexes as novel cis-elements controlling transcription during embryonic development. Nucleic Acids Res. 2016; 44(9):4163-73. PMC: 4872077. DOI: 10.1093/nar/gkw011. View

10.

Ribeyre C, Lopes J, Boule J, Piazza A, Guedin A, Zakian V . The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo. PLoS Genet. 2009; 5(5):e1000475. PMC: 2673046. DOI: 10.1371/journal.pgen.1000475. View

11.

Mendoza O, Bourdoncle A, Boule J, Brosh Jr R, Mergny J . G-quadruplexes and helicases. Nucleic Acids Res. 2016; 44(5):1989-2006. PMC: 4797304. DOI: 10.1093/nar/gkw079. View

12.

Davis J . G-quartets 40 years later: from 5'-GMP to molecular biology and supramolecular chemistry. Angew Chem Int Ed Engl. 2004; 43(6):668-98. DOI: 10.1002/anie.200300589. View

13.

Schiavone D, Guilbaud G, Murat P, Papadopoulou C, Sarkies P, Prioleau M . Determinants of G quadruplex-induced epigenetic instability in REV1-deficient cells. EMBO J. 2014; 33(21):2507-20. PMC: 4282387. DOI: 10.15252/embj.201488398. View

14.

Vannier J, Pavicic-Kaltenbrunner V, Petalcorin M, Ding H, Boulton S . RTEL1 dismantles T loops and counteracts telomeric G4-DNA to maintain telomere integrity. Cell. 2012; 149(4):795-806. DOI: 10.1016/j.cell.2012.03.030. View

15.

Shivalingam A, Izquierdo M, Le Marois A, Vysniauskas A, Suhling K, Kuimova M . The interactions between a small molecule and G-quadruplexes are visualized by fluorescence lifetime imaging microscopy. Nat Commun. 2015; 6:8178. PMC: 4579598. DOI: 10.1038/ncomms9178. View

16.

Zimmer J, Tacconi E, Folio C, Badie S, Porru M, Klare K . Targeting BRCA1 and BRCA2 Deficiencies with G-Quadruplex-Interacting Compounds. Mol Cell. 2016; 61(3):449-460. PMC: 4747901. DOI: 10.1016/j.molcel.2015.12.004. View

17.

McLuckie K, Di Antonio M, Zecchini H, Xian J, Caldas C, Krippendorff B . G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells. J Am Chem Soc. 2013; 135(26):9640-3. PMC: 3964824. DOI: 10.1021/ja404868t. View

18.

Rodriguez R, Miller K, Forment J, Bradshaw C, Nikan M, Britton S . Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. Nat Chem Biol. 2012; 8(3):301-10. PMC: 3433707. DOI: 10.1038/nchembio.780. View

19.

Biffi G, Tannahill D, McCafferty J, Balasubramanian S . Quantitative visualization of DNA G-quadruplex structures in human cells. Nat Chem. 2013; 5(3):182-6. PMC: 3622242. DOI: 10.1038/nchem.1548. View

20.

Johnson J, Cao K, Ryvkin P, Wang L, Johnson F . Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. Nucleic Acids Res. 2009; 38(4):1114-22. PMC: 2831322. DOI: 10.1093/nar/gkp1103. View