Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

The Interplay between G-quadruplex and Transcription

Author(s): Nayun Kim*

Volume 26, Issue 16, 2019

Page: [2898 - 2917] Pages: 20

DOI: 10.2174/0929867325666171229132619

open access plus


G4 DNA is a non-canonical DNA structure consisting of a stacked array of Gquartets held together by base pairing between guanine bases. The formation of G4 DNA requires a cluster of guanine-runs within a strand of DNA. Even though the chemistry of this remarkable DNA structure has been under investigation for decades, evidence supporting the biological relevance of G4 DNA has only begun to emerge and point to very important and conserved biological functions. This review will specifically focus on the interplay between transcription and G4 DNA and discuss two alternative but interconnected perspectives. The first part of the review will describe the evidence substantiating the intriguing idea that a shift in DNA structural conformation could be another layer of non-genetic or epigenetic regulator of gene expression and thereby an important determinant of cell fate. The second part will describe the recent genetic studies showing that those genomic loci containing G4 DNA-forming guanine-rich sequences are potential hotspots of genome instability and that the level and orientation of transcription is critical in the materialization of genome instability associated with these sequences.

Keywords: G4 DNA, transcription, R-loops, Top1, supercoiling, genome stability.

Sen, D.; Gilbert, W. Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature, 1988, 334(6180), 364-366. []. [PMID: 3393228].
Todd, A.K.; Johnston, M.; Neidle, S. Highly prevalent putative quadruplex sequence motifs in human DNA. Nucleic Acids Res., 2005, 33(9), 2901-2907. []. [PMID: 15914666].
Huppert, J.L.; Balasubramanian, S. Prevalence of quadruplexes in the human genome. Nucleic Acids Res., 2005, 33(9), 2908-2916. []. [PMID: 15914667].
Henderson, E.; Hardin, C.C.; Walk, S.K.; Tinoco, I., Jr; Blackburn, E.H. Telomeric DNA oligonucleotides form novel intramolecular structures containing guanine-guanine base pairs. Cell, 1987, 51(6), 899-908. []. [PMID: 3690664].
Fry, M. Tetraplex DNA and its interacting proteins, Frontiers in bio-science. J. Virt. Lib., 2007, 12, 4336-4351.
Huppert, J.L.; Balasubramanian, S. G-quadruplexes in promoters throughout the human genome. Nucleic Acids Res., 2007, 35(2), 406-413. []. [PMID: 17169996].
Du, Z.; Zhao, Y.; Li, N. Genome-wide colonization of gene regulatory elements by G4 DNA motifs. Nucleic Acids Res., 2009, 37(20), 6784-6798. []. [PMID: 19759215].
Du, Z.; Zhao, Y.; Li, N. Genome-wide analysis reveals regulatory role of G4 DNA in gene transcription. Genome Res., 2008, 18(2), 233-241. []. [PMID: 18096746].
Hershman, S.G.; Chen, Q.; Lee, J.Y.; Kozak, M.L.; Yue, P.; Wang, L.S.; Johnson, F.B. Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae. Nucleic Acids Res., 2008, 36(1), 144-156. []. [PMID: 17999996].
Capra, J.A.; Paeschke, K.; Singh, M.; Zakian, V.A. G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae. PLOS Comput. Biol., 2010, 6(7)e1000861 []. [PMID: 20676380].
Henderson, A.; Wu, Y.; Huang, Y.C.; Chavez, E.A.; Platt, J.; Johnson, F.B.; Brosh, R.M., Jr; Sen, D.; Lansdorp, P.M. Detection of G-quadruplex DNA in mammalian cells. Nucleic Acids Res., 2014, 42(2), 860-869. []. [PMID: 24163102].
Fernando, H.; Rodriguez, R.; Balasubramanian, S. Selective recognition of a DNA G-quadruplex by an engineered antibody. Biochemistry, 2008, 47(36), 9365-9371. []. [PMID: 18702511].
Biffi, G.; Tannahill, D.; McCafferty, J.; Balasubramanian, S. Quantitative visualization of DNA G-quadruplex structures in human cells. Nat. Chem., 2013, 5(3), 182-186. []. [PMID: 23422559].
Lam, E.Y.; Beraldi, D.; Tannahill, D.; Balasubramanian, S. G-quadruplex structures are stable and detectable in human genomic DNA. Nat. Commun., 2013, 4, 1796. []. [PMID: 23653208].
Hänsel-Hertsch, R.; Beraldi, D.; Lensing, S.V.; Marsico, G.; Zyner, K.; Parry, A.; Di Antonio, M.; Pike, J.; Kimura, H.; Narita, M.; Tannahill, D.; Balasubramanian, S. G-quadruplex structures mark human regulatory chromatin. Nat. Genet., 2016, 48(10), 1267-1272. []. [PMID: 27618450].
Liu, H.Y.; Zhao, Q.; Zhang, T.P.; Wu, Y.; Xiong, Y.X.; Wang, S.K.; Ge, Y.L.; He, J.H.; Lv, P.; Ou, T.M.; Tan, J.H.; Li, D.; Gu, L.Q.; Ren, J.; Zhao, Y.; Huang, Z.S. Conformation selective antibody enables genome profiling and leads to discovery of parallel G-quadruplex in human telomeres. Cell Chem. Biol., 2016, 23(10), 1261-1270. []. [PMID: 27693060].
Piazza, A.; Adrian, M.; Samazan, F.; Heddi, B.; Hamon, F.; Serero, A.; Lopes, J.; Teulade-Fichou, M.P.; Phan, A.T.; Nicolas, A. Short loop length and high thermal stability determine genomic instability induced by G-quadruplex-forming minisatellites. EMBO J., 2015, 34(12), 1718-1734. []. [PMID: 25956747].
Guédin, A.; Gros, J.; Alberti, P.; Mergny, J.L. How long is too long? Effects of loop size on G-quadruplex stability. Nucleic Acids Res., 2010, 38(21), 7858-7868. []. [PMID: 20660477].
Agrawal, P.; Lin, C.; Mathad, R.I.; Carver, M.; Yang, D. The major G-quadruplex formed in the human BCL-2 proximal promoter adopts a parallel structure with a 13-nt loop in K+ solution. J. Am. Chem. Soc., 2014, 136(5), 1750-1753. []. [PMID: 24450880].
Sun, D.; Hurley, L.H. Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. Methods Mol. Biol., 2010, 608, 65-79. []. [PMID: 20012416].
Williams, J.D.; Fleetwood, S.; Berroyer, A.; Kim, N.; Larson, E.D. Sites of instability in the human TCF3 (E2A) gene adopt G-quadruplex DNA structures in vitro. Front. Genet., 2015, 6, 177. []. [PMID: 26029241].
Kumari, R.; Nambiar, M.; Shanbagh, S.; Raghavan, S.C. Detection of G-quadruplex DNA using primer extension as a tool. PLoS One, 2015, 10(3)e0119722 []. [PMID: 25799152].
Belotserkovskii, B.P.; Neil, A.J.; Saleh, S.S.; Shin, J.H.; Mirkin, S.M.; Hanawalt, P.C. Transcription blockage by homopurine DNA sequences: Role of sequence composition and single-strand breaks. Nucleic Acids Res., 2013, 41(3), 1817-1828. []. [PMID: 23275544].
Belotserkovskii, B.P.; Liu, R.; Tornaletti, S.; Krasilnikova, M.M.; Mirkin, S.M.; Hanawalt, P.C. Mechanisms and implications of transcription blockage by guanine-rich DNA sequences. Proc. Natl. Acad. Sci. USA, 2010, 107(29), 12816-12821. []. [PMID: 20616059].
Broxson, C.; Beckett, J.; Tornaletti, S. Transcription arrest by a G quadruplex forming-trinucleotide repeat sequence from the human c-myb gene. Biochemistry, 2011, 50(19), 4162-4172. []. [PMID: 21469677].
Belotserkovskii, B.P.; Soo Shin, J.H.; Hanawalt, P.C. Strong transcription blockage mediated by R-loop formation within a G-rich homopurine-homopyrimidine sequence localized in the vicinity of the promoter. Nucleic Acids Res., 2017, 45(11), 6589-6599. []. [PMID: 28498974].
Zheng, K.W.; Xiao, S.; Liu, J.Q.; Zhang, J.Y.; Hao, Y.H.; Tan, Z. Co-transcriptional formation of DNA:RNA hybrid G-quadruplex and potential function as constitutional cis element for transcription control. Nucleic Acids Res., 2013, 41(10), 5533-5541. []. [PMID: 23585281].
Gilmour, D.S. Promoter proximal pausing on genes in metazoans. Chromosoma, 2009, 118(1), 1-10. []. [PMID: 18830703].
Eddy, J.; Vallur, A.C.; Varma, S.; Liu, H.; Reinhold, W.C.; Pommier, Y.; Maizels, N. G4 motifs correlate with promoter-proximal transcriptional pausing in human genes. Nucleic Acids Res., 2011, 39(12), 4975-4983. []. [PMID: 21371997].
Raiber, E.A.; Kranaster, R.; Lam, E.; Nikan, M.; Balasubramanian, S. A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro. Nucleic Acids Res., 2012, 40(4), 1499-1508. []. [PMID: 22021377].
Cogoi, S.; Paramasivam, M.; Membrino, A.; Yokoyama, K.K.; Xodo, L.E. The KRAS promoter responds to Myc-associated zinc finger and poly(ADP-ribose) polymerase 1 proteins, which recognize a critical quadruplex-forming GA-element. J. Biol. Chem., 2010, 285(29), 22003-22016. []. [PMID: 20457603].
Kerkour, A.; Marquevielle, J.; Ivashchenko, S.; Yatsunyk, L.A.; Mergny, J.L.; Salgado, G.F. High-resolution three-dimensional NMR structure of the KRAS proto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation. J. Biol. Chem., 2017, 292(19), 8082-8091. []. [PMID: 28330874].
Gao, J.; Zybailov, B.L.; Byrd, A.K.; Griffin, W.C.; Chib, S.; Mackintosh, S.G.; Tackett, A.J.; Raney, K.D. Yeast transcription co-activator Sub1 and its human homolog PC4 preferentially bind to G-quadruplex DNA. Chem. Commun. (Camb.), 2015, 51(33), 7242-7244. []. [PMID: 25813861].
Tajrishi, M.M.; Tuteja, R.; Tuteja, N. Nucleolin: The most abundant multifunctional phosphoprotein of nucleolus. Commun. Integr. Biol., 2011, 4(3), 267-275. []. [PMID: 21980556].
Yuan, J.; Muljo, S.A. Exploring the RNA world in hematopoietic cells through the lens of RNA-binding proteins. Immunol. Rev., 2013, 253(1), 290-303. []. [PMID: 23550653].
Berger, C.M.; Gaume, X.; Bouvet, P. The roles of nucleolin subcellular localization in cancer. Biochimie, 2015, 113, 78-85. []. [PMID: 25866190].
Otake, Y.; Soundararajan, S.; Sengupta, T.K.; Kio, E.A.; Smith, J.C.; Pineda-Roman, M.; Stuart, R.K.; Spicer, E.K.; Fernandes, D.J. Overexpression of nucleolin in chronic lymphocytic leukemia cells induces stabilization of bcl2 mRNA. Blood, 2007, 109(7), 3069-3075. [PMID: 17179226].
Hanakahi, L.A.; Sun, H.; Maizels, N. High affinity interactions of nucleolin with G-G-paired rDNA. J. Biol. Chem., 1999, 274(22), 15908-15912. []. [PMID: 10336496].
Dempsey, L.A.; Sun, H.; Hanakahi, L.A.; Maizels, N. G4 DNA binding by LR1 and its subunits, nucleolin and hnRNP D, A role for G-G pairing in immunoglobulin switch recombination. J. Biol. Chem., 1999, 274(2), 1066-1071. []. [PMID: 9873052].
Uribe, D.J.; Guo, K.; Shin, Y.J.; Sun, D. Heterogeneous nuclear ribonucleoprotein K and nucleolin as transcriptional activators of the vascular endothelial growth factor promoter through interaction with secondary DNA structures. Biochemistry, 2011, 50(18), 3796-3806. []. [PMID: 21466159].
Perrone, R.; Nadai, M.; Frasson, I.; Poe, J.A.; Butovskaya, E.; Smithgall, T.E.; Palumbo, M.; Palù, G.; Richter, S.N. A dynamic G-quadruplex region regulates the HIV-1 long terminal repeat promoter. J. Med. Chem., 2013, 56(16), 6521-6530. []. [PMID: 23865750].
Tosoni, E.; Frasson, I.; Scalabrin, M.; Perrone, R.; Butovskaya, E.; Nadai, M.; Palù, G.; Fabris, D.; Richter, S.N. Nucleolin stabilizes G-quadruplex structures folded by the LTR promoter and silences HIV-1 viral transcription. Nucleic Acids Res., 2015, 43(18), 8884-8897. []. [PMID: 26354862].
Siddiqui-Jain, A.; Grand, C.L.; Bearss, D.J.; Hurley, L.H. Direct evidence for a G-quadruplex in a promoter region and its targeting with a small molecule to repress c-MYC transcription. Proc. Natl. Acad. Sci. USA, 2002, 99(18), 11593-11598. []. [PMID: 12195017].
González, V.; Guo, K.; Hurley, L.; Sun, D. Identification and characterization of nucleolin as a c-myc G-quadruplex-binding protein. J. Biol. Chem., 2009, 284(35), 23622-23635. []. [PMID: 19581307].
González, V.; Hurley, L.H. The C-terminus of nucleolin promotes the formation of the c-MYC G-quadruplex and inhibits c-MYC promoter activity. Biochemistry, 2010, 49(45), 9706-9714. []. [PMID: 20932061].
Bai, L.; Morozov, A.V. Gene regulation by nucleosome positioning. Trends Genet., 2010, 26(11), 476-483. []. [PMID: 20832136].
Wong, H.M.; Huppert, J.L. Stable G-quadruplexes are found outside nucleosome-bound regions. Mol. Biosyst., 2009, 5(12), 1713-1719. []. [PMID: 19585004].
Halder, K.; Halder, R.; Chowdhury, S. Genome-wide analysis predicts DNA structural motifs as nucleosome exclusion signals. Mol. Biosyst., 2009, 5(12), 1703-1712. []. [PMID: 19587895].
Hogan, G.J.; Lee, C.K.; Lieb, J.D. Cell cycle-specified fluctuation of nucleosome occupancy at gene promoters. PLoS Genet., 2006, 2(9)e158 []. [PMID: 17002501].
Sun, H.; Karow, J.K.; Hickson, I.D.; Maizels, N. The Bloom’s syndrome helicase unwinds G4 DNA. J. Biol. Chem., 1998, 273(42), 27587-27592. []. [PMID: 9765292].
Nguyen, G.H.; Tang, W.; Robles, A.I.; Beyer, R.P.; Gray, L.T.; Welsh, J.A.; Schetter, A.J.; Kumamoto, K.; Wang, X.W.; Hickson, I.D.; Maizels, N.; Monnat, R.J., Jr; Harris, C.C. Regulation of gene expression by the BLM helicase correlates with the presence of G-quadruplex DNA motifs. Proc. Natl. Acad. Sci. USA, 2014, 111(27), 9905-9910. []. [PMID: 24958861].
Tang, W.; Robles, A.I.; Beyer, R.P.; Gray, L.T.; Nguyen, G.H.; Oshima, J.; Maizels, N.; Harris, C.C.; Monnat, R.J., Jr The Werner syndrome RECQ helicase targets G4 DNA in human cells to modulate transcription. Hum. Mol. Genet., 2016, 25(10), 2060-2069. []. [PMID: 26984941].
Smestad, J.A.; Maher, L.J. III Relationships between putative G-quadruplex-forming sequences, RecQ helicases, and transcription. BMC Med. Genet., 2015, 16, 91. []. [PMID: 26449372].
Johnson, J.E.; Cao, K.; Ryvkin, P.; Wang, L.S.; Johnson, F.B. Altered gene expression in the Werner and Bloom syndromes is associated with sequences having G-quadruplex forming potential. Nucleic Acids Res., 2010, 38(4), 1114-1122. []. [PMID: 19966276].
Romiguier, J.; Ranwez, V.; Douzery, E.J.; Galtier, N. Contrasting GC-content dynamics across 33 mammalian genomes: relationship with life-history traits and chromosome sizes. Genome Res., 2010, 20(8), 1001-1009. []. [PMID: 20530252].
David, A.P.; Margarit, E.; Domizi, P.; Banchio, C.; Armas, P.; Calcaterra, N.B. G-quadruplexes as novel cis-elements controlling transcription during embryonic development. Nucleic Acids Res., 2016, 44(9), 4163-4173. []. [PMID: 26773060].
Monchaud, D.; Granzhan, A.; Saettel, N.; Guédin, A.; Mergny, J.L.; Teulade-Fichou, M.P. One ring to bind them all ”-part I: the efficiency of the macrocyclic scaffold for gquadruplex DNA recognition. J. Nucleic Acids, 2010.2010, pii. 525862. [] [PMID: 20725629]
Yadav, V. Hemansi; Kim, N.; Tuteja, N.; Yadav, P. G Quadruplex in plants: A ubiquitous regulatory element and its biological relevance. Front. Plant Sci., 2017, 8, 1163. []. [PMID: 28725233].
Mullen, M.A.; Olson, K.J.; Dallaire, P.; Major, F.; Assmann, S.M.; Bevilacqua, P.C. RNA G-Quadruplexes in the model plant species Arabidopsis thaliana: prevalence and possible functional roles. Nucleic Acids Res., 2010, 38(22), 8149-8163. []. [PMID: 20860998].
Andorf, C.M.; Kopylov, M.; Dobbs, D.; Koch, K.E.; Stroupe, M.E.; Lawrence, C.J.; Bass, H.W. G-quadruplex (G4) motifs in the maize (Zea mays L.) genome are enriched at specific locations in thousands of genes coupled to energy status, hypoxia, low sugar, and nutrient deprivation. J. Genet. Genomics, 2014, 41(12), 627-647. []. [PMID: 25527104].
Garg, R.; Aggarwal, J.; Thakkar, B. Genome-wide discovery of G-quadruplex forming sequences and their functional relevance in plants. Sci. Rep., 2016, 6, 28211. []. [PMID: 27324275].
Qin, Y.; Hurley, L.H. Structures, folding patterns, and functions of intramolecular DNA G-quadruplexes found in eukaryotic promoter regions. Biochimie, 2008, 90(8), 1149-1171. []. [PMID: 18355457].
Yang, D.; Hurley, L.H. Structure of the biologically relevant G-quadruplex in the c-MYC promoter. Nucleosides Nucleotides Nucleic Acids, 2006, 25(8), 951-968. []. [PMID: 16901825].
Cogoi, S.; Xodo, L.E. G-quadruplex formation within the promoter of the KRAS proto-oncogene and its effect on transcription. Nucleic Acids Res., 2006, 34(9), 2536-2549. []. [PMID: 16687659].
Dexheimer, T.S.; Sun, D.; Hurley, L.H. Deconvoluting the structural and drug-recognition complexity of the G-quadruplex-forming region upstream of the bcl-2 P1 promoter. J. Am. Chem. Soc., 2006, 128(16), 5404-5415. []. [PMID: 16620112].
Dai, J.; Dexheimer, T.S.; Chen, D.; Carver, M.; Ambrus, A.; Jones, R.A.; Yang, D. An intramolecular G-quadruplex structure with mixed parallel/antiparallel G-strands formed in the human BCL-2 promoter region in solution. J. Am. Chem. Soc., 2006, 128(4), 1096-1098. []. [PMID: 16433524].
Nambiar, M.; Goldsmith, G.; Moorthy, B.T.; Lieber, M.R.; Joshi, M.V.; Choudhary, B.; Hosur, R.V.; Raghavan, S.C. Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma. Nucleic Acids Res., 2011, 39(3), 936-948. []. [PMID: 20880994].
Eddy, J.; Maizels, N. Gene function correlates with potential for G4 DNA formation in the human genome. Nucleic Acids Res., 2006, 34(14), 3887-3896. []. [PMID: 16914419].
Wei, C.; Wang, L.; Jia, G.; Zhou, J.; Han, G.; Li, C. The binding mode of porphyrins with cation side arms to (TG4T)4 G-quadruplex: spectroscopic evidence. Biophys. Chem., 2009, 143(1-2), 79-84. []. [PMID: 19411133].
Jia, G.; Feng, Z.; Wei, C.; Zhou, J.; Wang, X.; Li, C. Dynamic insight into the interaction between porphyrin and G-quadruplex DNAs: time-resolved fluorescence anisotropy study. J. Phys. Chem. B, 2009, 113(50), 16237-16245. []. [PMID: 19924868].
Chen, B.J.; Wu, Y.L.; Tanaka, Y.; Zhang, W. Small molecules targeting c-Myc oncogene: promising anti-cancer therapeutics. Int. J. Biol. Sci., 2014, 10(10), 1084-1096. []. [PMID: 25332683].
Moruno-Manchon, J.F.; Koellhoffer, E.C.; Gopakumar, J.; Hambarde, S.; Kim, N.; McCullough, L.D.; Tsvetkov, A.S. The G-quadruplex DNA stabilizing drug pyridostatin promotes DNA damage and downregulates transcription of Brca1 in neurons. Aging (Albany NY), 2017, 9(9), 1957-1970. []. [PMID: 28904242].
Edwards, T.K.; Saleem, A.; Shaman, J.A.; Dennis, T.; Gerigk, C.; Oliveros, E.; Gartenberg, M.R.; Rubin, E.H. Role for nucleolin/Nsr1 in the cellular localization of topoisomerase I. J. Biol. Chem., 2000, 275(46), 36181-36188. []. [PMID: 10967121].
Bates, P.J.; Reyes-Reyes, E.M.; Malik, M.T.; Murphy, E.M.; O’Toole, M.G.; Trent, J.O. G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms. Biochim. Biophys. Acta, 2016. [PMID: 28007579].
Palmieri, D.; Richmond, T.; Piovan, C.; Sheetz, T.; Zanesi, N.; Troise, F.; James, C.; Wernicke, D.; Nyei, F.; Gordon, T.J.; Consiglio, J.; Salvatore, F.; Coppola, V.; Pichiorri, F.; De Lorenzo, C.; Croce, C.M. Human anti-nucleolin recombinant immunoagent for cancer therapy. Proc. Natl. Acad. Sci. USA, 2015, 112(30), 9418-9423. []. [PMID: 26170308].
Bates, P.J.; Laber, D.A.; Miller, D.M.; Thomas, S.D.; Trent, J.O. Discovery and development of the G-rich oligonucleotide AS1411 as a novel treatment for cancer. Exp. Mol. Pathol., 2009, 86(3), 151-164. []. [PMID: 19454272].
Teng, Y.; Girvan, A.C.; Casson, L.K.; Pierce, W.M., Jr; Qian, M.; Thomas, S.D.; Bates, P.J. AS1411 alters the localization of a complex containing protein arginine methyltransferase 5 and nucleolin. Cancer Res., 2007, 67(21), 10491-10500. []. [PMID: 17974993].
Cheng, Y.; Zhao, G.; Zhang, S.; Nigim, F.; Zhou, G.; Yu, Z.; Song, Y.; Chen, Y.; Li, Y. AS1411-Induced Growth Inhibition of Glioma Cells by Up-Regulation of p53 and Down-Regulation of Bcl-2 and Akt1 via Nucleolin. PLoS One, 2016, 11(12)e0167094 []. [PMID: 27907160].
Soundararajan, S.; Chen, W.; Spicer, E.K.; Courtenay-Luck, N.; Fernandes, D.J. The nucleolin targeting aptamer AS1411 destabilizes Bcl-2 messenger RNA in human breast cancer cells. Cancer Res., 2008, 68(7), 2358-2365. []. [PMID: 18381443].
Mirkin, E.V.; Mirkin, S.M. Replication fork stalling at natural impediments. Microbiol. Mol. Biol. Rev., 2007, 71(1), 13-35. []. [PMID: 17347517].
Su, X.A.; Dion, V.; Gasser, S.M.; Freudenreich, C.H. Regulation of recombination at yeast nuclear pores controls repair and triplet repeat stability. Genes Dev., 2015, 29(10), 1006-1017. []. [PMID: 25940904].
Kim, H-M.; Narayanan, V.; Mieczkowski, P.A.; Petes, T.D.; Krasilnikova, M.M.; Mirkin, S.M.; Lobachev, K.S. Chromosome fragility at GAA tracts in yeast depends on repeat orientation and requires mismatch repair. EMBO J., 2008, 27(21), 2896-2906. []. [PMID: 18833189].
Tang, W.; Dominska, M.; Greenwell, P.W.; Harvanek, Z.; Lobachev, K.S.; Kim, H.M.; Narayanan, V.; Mirkin, S.M.; Petes, T.D. Friedreich’s ataxia (GAA)n•(TTC)n repeats strongly stimulate mitotic crossovers in Saccharomyces cerevisae. PLoS Genet., 2011, 7(1)e1001270 []. [PMID: 21249181].
Piazza, A.; Serero, A.; Boulé, J.B.; Legoix-Né, P.; Lopes, J.; Nicolas, A. Stimulation of gross chromosomal rearrangements by the human CEB1 and CEB25 minisatellites in Saccharomyces cerevisiae depends on G-quadruplexes or Cdc13. PLoS Genet., 2012, 8(11)e1003033 []. [PMID: 23133402].
Ribeyre, C.; Lopes, J.; Boulé, J.B.; Piazza, A.; Guédin, A.; Zakian, V.A.; Mergny, J.L.; Nicolas, A. The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo. PLoS Genet., 2009, 5(5)e1000475 []. [PMID: 19424434].
McLuckie, K.I.; Di Antonio, M.; Zecchini, H.; Xian, J.; Caldas, C.; Krippendorff, B.F.; Tannahill, D.; Lowe, C.; Balasubramanian, S. G-quadruplex DNA as a molecular target for induced synthetic lethality in cancer cells. J. Am. Chem. Soc., 2013, 135(26), 9640-9643. []. [PMID: 23782415].
Piazza, A.; Boulé, J.B.; Lopes, J.; Mingo, K.; Largy, E.; Teulade-Fichou, M.P.; Nicolas, A. Genetic instability triggered by G-quadruplex interacting Phen-DC compounds in Saccharomyces cerevisiae. Nucleic Acids Res., 2010, 38(13), 4337-4348. []. [PMID: 20223771].
Rodriguez, R.; Miller, K.M.; Forment, J.V.; Bradshaw, C.R.; Nikan, M.; Britton, S.; Oelschlaegel, T.; Xhemalce, B.; Balasubramanian, S.; Jackson, S.P. Small-molecule-induced DNA damage identifies alternative DNA structures in human genes. Nat. Chem. Biol., 2012, 8(3), 301-310. []. [PMID: 22306580].
Kim, N.; Jinks-Robertson, S. Transcription as a source of genome instability. Nat. Rev. Genet., 2012, 13(3), 204-214. []. [PMID: 22330764].
Aguilera, A.; Gaillard, H. Transcription and recombination: when RNA meets DNA. Cold Spring Harb. Perspect. Biol., 2014, 6(8), 6. []. [PMID: 25085910].
Azvolinsky, A.; Giresi, P.G.; Lieb, J.D.; Zakian, V.A. Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae. Mol. Cell, 2009, 34(6), 722-734. []. [PMID: 19560424].
Freedman, J.A.; Jinks-Robertson, S. Genetic requirements for spontaneous and transcription-stimulated mitotic recombination in Saccharomyces cerevisiae. Genetics, 2002, 162(1), 15-27. [PMID: 12242220].
Kim, N.; Abdulovic, A.L.; Gealy, R.; Lippert, M.J.; Jinks-Robertson, S. Transcription-associated mutagenesis in yeast is directly proportional to the level of gene expression and influenced by the direction of DNA replication. DNA Repair (Amst.), 2007, 6(9), 1285-1296. []. [PMID: 17398168].
Sun, D.; Hurley, L.H. 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), 2863-2874. []. [PMID: 19385599].
Duquette, M.L.; Handa, P.; Vincent, J.A.; Taylor, A.F.; Maizels, N. Intracellular transcription of G-rich DNAs induces formation of G-loops, novel structures containing G4 DNA. Genes Dev., 2004, 18(13), 1618-1629. []. [PMID: 15231739].
Cheung, I.; Schertzer, M.; Rose, A.; Lansdorp, P.M. Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA. Nat. Genet., 2002, 31(4), 405-409. []. [PMID: 12101400].
Bacolla, A.; Tainer, J.A.; Vasquez, K.M.; Cooper, D.N. Translocation and deletion breakpoints in cancer genomes are associated with potential non-B DNA-forming sequences. Nucleic Acids Res., 2016, 44(12), 5673-5688. []. [PMID: 27084947].
Katapadi, V.K.; Nambiar, M.; Raghavan, S.C. Potential G-quadruplex formation at breakpoint regions of chromosomal translocations in cancer may explain their fragility. Genomics, 2012, 100(2), 72-80. []. [PMID: 22659239].
Nambiar, M.; Srivastava, M.; Gopalakrishnan, V.; Sankaran, S.K.; Raghavan, S.C. G-quadruplex structures formed at the HOX11 breakpoint region contribute to its fragility during t(10;14) translocation in T-cell leukemia. Mol. Cell. Biol., 2013, 33(21), 4266-4281. []. [PMID: 24001773].
Kim, N.; Jinks-Robertson, S. Guanine repeat-containing sequences confer transcription-dependent instability in an orientation-specific manner in yeast DNA Repair (Amst), 2011.
Pommier, Y.; Sun, Y.; Huang, S.N.; Nitiss, J.L. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat. Rev. Mol. Cell Biol., 2016, 17(11), 703-721. []. [PMID: 27649880].
Kim, N.; Jinks-Robertson, S. The Top1 paradox: Friend and foe of the eukaryotic genome DNA Repair (Amst) 2017.
Wu, H.Y.; Shyy, S.H.; Wang, J.C.; Liu, L.F. Transcription generates positively and negatively supercoiled domains in the template. Cell, 1988, 53(3), 433-440. []. [PMID: 2835168].
Mirkin, S.M. Discovery of alternative DNA structures: A heroic decade (1979-1989). Front. Biosci., 2008, 13, 1064-1071.
Conover, H.N.; Lujan, S.A.; Chapman, M.J.; Cornelio, D.A.; Sharif, R.; Williams, J.S.; Clark, A.B.; Camilo, F.; Kunkel, T.A.; Argueso, J.L. Stimulation of Chromosomal Rearrangements by Ribonucleotides. Genetics, 2015, 201(3), 951-961. []. [PMID: 26400612].
Andersen, S.L.; Sloan, R.S.; Petes, T.D.; Jinks-Robertson, S. Genome-destabilizing effects associated with top1 loss or accumulation of top1 cleavage complexes in yeast. PLoS Genet., 2015, 11(4)e1005098 []. [PMID: 25830313].
Allen-Soltero, S.; Martinez, S.L.; Putnam, C.D.; Kolodner, R.D. A saccharomyces cerevisiae RNase H2 interaction network functions to suppress genome instability. Mol. Cell. Biol., 2014, 34(8), 1521-1534. []. [PMID: 24550002].
Huertas, P.; Aguilera, A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol. Cell, 2003, 12(3), 711-721. []. [PMID: 14527416].
Li, X.; Manley, J.L. Cotranscriptional processes and their influence on genome stability. Genes Dev., 2006, 20(14), 1838-1847. []. [PMID: 16847344].
Yadav, P.; Harcy, V.; Argueso, J.L.; Dominska, M.; Jinks-Robertson, S.; Kim, N. Topoisomerase I plays a critical role in suppressing genome instability at a highly transcribed G-quadruplex-forming sequence. PLoS Genet., 2014, 10(12)e1004839 []. [PMID: 25473964].
Yadav, P.; Owiti, N.; Kim, N. The role of topoisomerase I in suppressing genome instability associated with a highly transcribed guanine-rich sequence is not restricted to preventing RNA:DNA hybrid accumulation. Nucleic Acids Res., 2016, 44(2), 718-729. []. [PMID: 26527723].
Lopez, C.R.; Singh, S.; Hambarde, S.; Griffin, W.C.; Gao, J.; Chib, S.; Yu, Y.; Ira, G.; Raney, K.D.; Kim, N. Yeast Sub1 and human PC4 are G-quadruplex binding proteins that suppress genome instability at co-transcriptionally formed G4 DNA. Nucleic Acids Res., 2017, 45(10), 5850-5862. []. [PMID: 28369605].
Shuai, L.; Deng, M.; Zhang, D.; Zhou, Y.; Zhou, X. Quadruplex-duplex motifs as new topoisomerase I inhibitors. Nucleosides Nucleotides Nucleic Acids, 2010, 29(11), 841-853. []. [PMID: 21128171].
Arimondo, P.B.; Riou, J.F.; Mergny, J.L.; Tazi, J.; Sun, J.S.; Garestier, T.; Hélène, C. Interaction of human DNA topoisomerase I with G-quartet structures. Nucleic Acids Res., 2000, 28(24), 4832-4838. []. [PMID: 11121473].
Marchand, C.; Pourquier, P.; Laco, G.S.; Jing, N.; Pommier, Y. Interaction of human nuclear topoisomerase I with guanosine quartet-forming and guanosine-rich single-stranded DNA and RNA oligonucleotides. J. Biol. Chem., 2002, 277(11), 8906-8911. []. [PMID: 11756434].
Kato, L.; Stanlie, A.; Begum, N.A.; Kobayashi, M.; Aida, M.; Honjo, T. An evolutionary view of the mechanism for immune and genome diversity. J. Immunol., 2012, 188(8), 3559-3566. []. [PMID: 22492685].
Chaudhuri, J.; Alt, F.W. Class-switch recombination: interplay of transcription, DNA deamination and DNA repair. Nat. Rev. Immunol., 2004, 4(7), 541-552. []. [PMID: 15229473].
Revy, P.; Muto, T.; Levy, Y.; Geissmann, F.; Plebani, A.; Sanal, O.; Catalan, N.; Forveille, M.; Dufourcq-Labelouse, R.; Gennery, A.; Tezcan, I.; Ersoy, F.; Kayserili, H.; Ugazio, A.G.; Brousse, N.; Muramatsu, M.; Notarangelo, L.D.; Kinoshita, K.; Honjo, T.; Fischer, A.; Durandy, A. Activation-induced cytidine deaminase (AID) deficiency causes the autosomal recessive form of the Hyper-IgM syndrome (HIGM2). Cell, 2000, 102(5), 565-575. []. [PMID: 11007475].
Muramatsu, M.; Kinoshita, K.; Fagarasan, S.; Yamada, S.; Shinkai, Y.; Honjo, T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell, 2000, 102(5), 553-563. []. [PMID: 11007474].
Bergsagel, P.L.; Chesi, M.; Nardini, E.; Brents, L.A.; Kirby, S.L.; Kuehl, W.M. Promiscuous translocations into immunoglobulin heavy chain switch regions in multiple myeloma. Proc. Natl. Acad. Sci. USA, 1996, 93(24), 13931-13936. []. [PMID: 8943038].
Küppers, R.; Dalla-Favera, R. Mechanisms of chromosomal translocations in B cell lymphomas. Oncogene, 2001, 20(40), 5580-5594. []. [PMID: 11607811].
Stavnezer, J.; Amemiya, C.T. Evolution of isotype switching. Semin. Immunol., 2004, 16(4), 257-275. []. [PMID: 15522624].
Bottaro, A.; Lansford, R.; Xu, L.; Zhang, J.; Rothman, P.; Alt, F.W. S region transcription per se promotes basal IgE class switch recombination but additional factors regulate the efficiency of the process. EMBO J., 1994, 13(3), 665-674. []. [PMID: 8313911].
Reaban, M.E.; Lebowitz, J.; Griffin, J.A. Transcription induces the formation of a stable RNA.DNA hybrid in the immunoglobulin alpha switch region. J. Biol. Chem., 1994, 269(34), 21850-21857. [PMID: 8063829].
Yu, K.; Chedin, F.; Hsieh, C.L.; Wilson, T.E.; Lieber, M.R. R-loops at immunoglobulin class switch regions in the chromosomes of stimulated B cells. Nat. Immunol., 2003, 4(5), 442-451. []. [PMID: 12679812].
Roy, D.; Yu, K.; Lieber, M.R. Mechanism of R-loop formation at immunoglobulin class switch sequences. Mol. Cell. Biol., 2008, 28(1), 50-60. []. [PMID: 17954560].
Maizels, N.; Gray, L.T. The G4 genome. PLoS Genet., 2013, 9(4)e1003468 []. [PMID: 23637633].
Kobayashi, M.; Aida, M.; Nagaoka, H.; Begum, N.A.; Kitawaki, Y.; Nakata, M.; Stanlie, A.; Doi, T.; Kato, L.; Okazaki, I.M.; Shinkura, R.; Muramatsu, M.; Kinoshita, K.; Honjo, T. AID-induced decrease in topoisomerase 1 induces DNA structural alteration and DNA cleavage for class switch recombination. Proc. Natl. Acad. Sci. USA, 2009, 106(52), 22375-22380. []. [PMID: 20018730].
Kobayashi, M.; Sabouri, Z.; Sabouri, S.; Kitawaki, Y.; Pommier, Y.; Abe, T.; Kiyonari, H.; Honjo, T. Decrease in topoisomerase I is responsible for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation. Proc. Natl. Acad. Sci. USA, 2011, 108(48), 19305-19310. []. [PMID: 22080610].
Larson, E.D.; Duquette, M.L.; Cummings, W.J.; Streiff, R.J.; Maizels, N. MutSalpha binds to and promotes synapsis of transcriptionally activated immunoglobulin switch regions. Curr. Biol., 2005, 15(5), 470-474. []. [PMID: 15753043].
Cahoon, L.A.; Seifert, H.S. An alternative DNA structure is necessary for pilin antigenic variation in Neisseria gonorrhoeae. Science, 2009, 325(5941), 764-767. []. [PMID: 19661435].
Cahoon, L.A.; Seifert, H.S. Transcription of a cis-acting, noncoding, small RNA is required for pilin antigenic variation in Neisseria gonorrhoeae. PLoS Pathog., 2013, 9(1)e1003074 []. [PMID: 23349628].
Norris, S.J. vls Antigenic variation systems of lyme disease borrelia: eluding host immunity through both random, segmental gene conversion and framework heterogeneity. Microbiol. Spectr., 2014, 2(6), 2. [PMID: 26104445].
Zhang, J.R.; Norris, S.J. Genetic variation of the Borrelia burgdorferi gene vlsE involves cassette-specific, segmental gene conversion. Infect. Immun., 1998, 66(8), 3698-3704. [PMID: 9673251].
Lin, T.; Gao, L.; Edmondson, D.G.; Jacobs, M.B.; Philipp, M.T.; Norris, S.J. Central role of the Holliday junction helicase RuvAB in vlsE recombination and infectivity of Borrelia burgdorferi. PLoS Pathog., 2009, 5(12)e1000679 []. [PMID: 19997622].
Walia, R.; Chaconas, G. Suggested role for G4 DNA in recombinational switching at the antigenic variation locus of the Lyme disease spirochete. PLoS One, 2013, 8(2)e57792 []. [PMID: 23469068].
Lin, Y.; Hubert, L., Jr; Wilson, J.H. Transcription destabilizes triplet repeats. Mol. Carcinog., 2009, 48(4), 350-361. []. [PMID: 18973172].
Lin, Y.; Dent, S.Y.; Wilson, J.H.; Wells, R.D.; Napierala, M. R loops stimulate genetic instability of CTG.CAG repeats. Proc. Natl. Acad. Sci. USA, 2010, 107(2), 692-697. []. [PMID: 20080737].
Nolin, S.L.; Brown, W.T.; Glicksman, A.; Houck, G.E., Jr; Gargano, A.D.; Sullivan, A.; Biancalana, V.; Bröndum-Nielsen, K.; Hjalgrim, H.; Holinski-Feder, E.; Kooy, F.; Longshore, J.; Macpherson, J.; Mandel, J.L.; Matthijs, G.; Rousseau, F.; Steinbach, P.; Väisänen, M.L.; von Koskull, H.; Sherman, S.L. Expansion of the fragile X CGG repeat in females with premutation or intermediate alleles. Am. J. Hum. Genet., 2003, 72(2), 454-464. []. [PMID: 12529854].
Haeusler, A.R.; Donnelly, C.J.; Periz, G.; Simko, E.A.; Shaw, P.G.; Kim, M.S.; Maragakis, N.J.; Troncoso, J.C.; Pandey, A.; Sattler, R.; Rothstein, J.D.; Wang, J. C9orf72 nucleotide repeat structures initiate molecular cascades of disease. Nature, 2014, 507(7491), 195-200. []. [PMID: 24598541].

© 2024 Bentham Science Publishers | Privacy Policy