Fundamentals of G-quadruplex Biology

Overview

Journal Annu Rep Med Chem

Specialty Biochemistry

Date 2020 Aug 25

PMID 32836507

Citations 9

Authors

F Brad Johnson

Affiliations

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Abstract

Several decades elapsed between the first descriptions of G-quadruplex nucleic acid structures (G4s) assembled and the emergence of experimental findings indicating that such structures can form and function in living systems. A large body of evidence now supports roles for G4s in many aspects of nucleic acid biology, spanning processes from transcription and chromatin structure, mRNA processing, protein translation, DNA replication and genome stability, and telomere and mitochondrial function. Nonetheless, it must be acknowledged that some of this evidence is tentative, which is not surprising given the technical challenges associated with demonstrating G4s in biology. Here I provide an overview of evidence for G4 biology, focusing particularly on the many potential pitfalls that can be encountered in its investigation, and briefly discuss some of broader biological processes that may be impacted by G4s including cancer.

Citing Articles

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References

Morse R . RAP, RAP, open up! New wrinkles for RAP1 in yeast. Trends Genet. 2000; 16(2):51-3. DOI: 10.1016/s0168-9525(99)01936-8. View

Gomez D, Armando R, Cerrudo C, Ghiringhelli P, Gomez D . Telomerase as a Cancer Target. Development of New Molecules. Curr Top Med Chem. 2016; 16(22):2432-40. PMC: 4997958. DOI: 10.2174/1568026616666160212122425. View

Li Y, Geyer C, Sen D . Recognition of anionic porphyrins by DNA aptamers. Biochemistry. 1996; 35(21):6911-22. DOI: 10.1021/bi960038h. View

Koole W, van Schendel R, Karambelas A, van Heteren J, Okihara K, Tijsterman M . A Polymerase Theta-dependent repair pathway suppresses extensive genomic instability at endogenous G4 DNA sites. Nat Commun. 2014; 5:3216. DOI: 10.1038/ncomms4216. View

Fernando H, Rodriguez R, Balasubramanian S . Selective recognition of a DNA G-quadruplex by an engineered antibody. Biochemistry. 2008; 47(36):9365-71. PMC: 2746966. DOI: 10.1021/bi800983u. 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

Mukherjee A, Sharma S, Sengupta S, Saha D, Kumar P, Hussain T . Telomere length-dependent transcription and epigenetic modifications in promoters remote from telomere ends. PLoS Genet. 2018; 14(11):e1007782. PMC: 6264879. DOI: 10.1371/journal.pgen.1007782. View

Cheong V, Heddi B, Lech C, Phan A . Xanthine and 8-oxoguanine in G-quadruplexes: formation of a G·G·X·O tetrad. Nucleic Acids Res. 2015; 43(21):10506-14. PMC: 4666386. DOI: 10.1093/nar/gkv826. View

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

10.

Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J . Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol. 2003; 5(8):741-7. PMC: 4940195. DOI: 10.1038/ncb1024. View

11.

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

12.

Mirihana Arachchilage G, Hetti Arachchilage M, Venkataraman A, Piontkivska H, Basu S . Stable G-quadruplex enabling sequences are selected against by the context-dependent codon bias. Gene. 2019; 696:149-161. DOI: 10.1016/j.gene.2019.02.006. View

13.

Piazza A, Adrian M, Samazan F, Heddi B, Hamon F, Serero A . Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites. EMBO J. 2015; 34(12):1718-34. PMC: 4475404. DOI: 10.15252/embj.201490702. View

14.

Halder R, Halder K, Sharma P, Garg G, Sengupta S, Chowdhury S . Guanine quadruplex DNA structure restricts methylation of CpG dinucleotides genome-wide. Mol Biosyst. 2010; 6(12):2439-47. DOI: 10.1039/c0mb00009d. View

15.

Biffi G, Tannahill D, Miller J, Howat W, Balasubramanian S . Elevated levels of G-quadruplex formation in human stomach and liver cancer tissues. PLoS One. 2014; 9(7):e102711. PMC: 4102534. DOI: 10.1371/journal.pone.0102711. View

16.

Todd A, Johnston M, Neidle S . Highly prevalent putative quadruplex sequence motifs in human DNA. Nucleic Acids Res. 2005; 33(9):2901-7. PMC: 1140077. DOI: 10.1093/nar/gki553. View

17.

Phan A, Kuryavyi V, Gaw H, Patel D . Small-molecule interaction with a five-guanine-tract G-quadruplex structure from the human MYC promoter. Nat Chem Biol. 2006; 1(3):167-73. PMC: 4690526. DOI: 10.1038/nchembio723. View

18.

Hardin C, Perry A, White K . Thermodynamic and kinetic characterization of the dissociation and assembly of quadruplex nucleic acids. Biopolymers. 2001; 56(3):147-94. DOI: 10.1002/1097-0282(2000/2001)56:3<147::AID-BIP10011>3.0.CO;2-N. View

19.

Oliveira P, Lobato da Silva C, Cabral J . An appraisal of human mitochondrial DNA instability: new insights into the role of non-canonical DNA structures and sequence motifs. PLoS One. 2013; 8(3):e59907. PMC: 3612095. DOI: 10.1371/journal.pone.0059907. View

20.

Lord C, Ashworth A . PARP inhibitors: Synthetic lethality in the clinic. Science. 2017; 355(6330):1152-1158. PMC: 6175050. DOI: 10.1126/science.aam7344. View