DNA Replication through G-Quadruplex Motifs Is Promoted by the Saccharomyces cerevisiae Pif1 DNA Helicase
Open accessAbstract
G-quadruplex (G4) DNA structures are extremely stable four-stranded secondary structures held together by noncanonical G-G base pairs. Genome-wide chromatin immunoprecipitation was used to determine the in vivo binding sites of the multifunctional Saccharomyces cerevisiae Pif1 DNA helicase, a potent unwinder of G4 structures in vitro. G4 motifs were a significant subset of the high-confidence Pif1-binding sites. Replication slowed in the vicinity of these motifs, and they were prone to breakage in Pif1-deficient cells, whereas non-G4 Pif1-binding sites did not show this behavior. Introducing many copies of G4 motifs caused slow growth in replication-stressed Pif1-deficient cells, which was relieved by spontaneous mutations that eliminated their ability to form G4 structures, bind Pif1, slow DNA replication, and stimulate DNA breakage. These data suggest that G4 structures form in vivo and that they are resolved by Pif1 to prevent replication fork stalling and DNA breakage.
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Deregulated G4 formation is a major driver of genomic instability.
“there is strong evidence that deregulated G4-formation is a major driver of genomic instability”
From G-quadruplex-mediated genomic instability drives SNVs in cancer (2024) · cites this paper as [34]
The Introduction reports that unresolved G4 structures can impede replication and cause chromosome breakage in Pif1-deficient yeast. The Results also show elevated recombination at G4 motifs in pif1Δ cells. These findings support a link to genomic instability under those conditions, but do not establish deregulated G4 formation as a major driver of genomic instability generally. (LLM, conf=0.87)
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Cites
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482 · see citing works
Pif1p Helicase, a Catalytic Inhibitor of Telomerase in Yeast
Zhou, J.-Q., Monson, E. K., Teng, S.-C., Schulz, V. P., & Zakian, V. A. (2000) · Science · doi:10.1126/science.289.5480.771 · Cited by 236 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 35
- Azvolinsky A Dunaway S Torres J Bessler J Zakian VA 2006 The S. cerevisiae Rrm3p DNA helicase moves with the replication fork and affects replication of all yeast chromosomes Genes Dev 20 3104 3116 17114583 PMC1635146
- Azvolinsky A Giresi P Lieb J Zakian V 2009 Highly transcribed RNA polymerase II genes are impediments to replication fork progression in Saccharomyces cerevisiae Mol Cell 34 722 734 19560424 PMC2728070
- Bochman ML Sabouri N Zakian VA 2010 Unwinding the functions of the Pif1 family helicases DNA Repair (Amst) 9 237 249 20097624 PMC2853725
- Boule J Vega L Zakian V 2005 The Yeast Pif1p helicase removes telomerase from DNA Nature 438 57 61 16121131
- Boule JB Zakian VA 2007 The yeast Pif1p DNA helicase preferentially unwinds RNA DNA substrates Nucleic Acids Res 35 5809 5818 17720711 PMC2034482
- Brewer BJ Fangman WL 1987 The localization of replication origins on ARS plasmids in S. cerevisiae Cell 51 463 471 2822257
- Buck MJ Nobel AB Lieb JD 2005 ChIPOTle: a user-friendly tool for the analysis of ChIP-chip data Genome Biol 6 R97 16277752 PMC1297653
- Capra JA Paeschke K Singh M Zakian VA 2010 G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae PLoS Comput Biol 6 e1000861 20676380 PMC2908698
- Cheung I Schertzer M Rose A Lansdorp PM 2002 Disruption of dog-1 in Caenorhabditis elegans triggers deletions upstream of guanine-rich DNA Nat Genet 31 405 409 12101400
- Deshpande AM Newlon CS 1996 DNA replication fork pause sites dependent on transcription Science 272 1030 1033 8638128
- Downs JA Lowndes NF Jackson SP 2000 A role for Saccharomyces cerevisiae histone H2A in DNA repair Nature 408 1001 1004 11140636
- Foury F Dyck EV 1985 A PIF-dependent recombinogenic signal in the mitochondrial DNA of yeast EMBO J 4 3525 3530 16453651 PMC554692
- Freudenreich CH Kantrow SM Zakian VA 1998 Expansion and length-dependent fragility of CTG repeats in yeast Science 279 853 856 9452383
- Gasser R Koller T Sogo JM 1996 The stability of nucleosomes at the replication fork J Mol Biol 258 224 239 8627621
- Greenfeder SA Newlon CS 1992 Replication forks pause at yeast centromeres Mol Cell Biol 12 4056 4066 1508202 PMC360298
- Hershman SG Chen Q Lee JY Kozak ML Yue P Wang LS Johnson FB 2008 Genomic distribution and functional analyses of potential G-quadruplex-forming sequences in Saccharomyces cerevisiae Nucleic Acids Res 36 144 156 17999996 PMC2248735
- Huppert JL 2008 Hunting G-quadruplexes Biochimie 90 1140 1148 18294969
- Huppert JL 2010 Structure, location and interactions of G-quadruplexes FEBS J 20670279
- Ivessa AS Lenzmeier BA Bessler JB Goudsouzian LK Schnakenberg SL Zakian VA 2003 The Saccharomyces cerevisiae helicase Rrm3p facilitates replication past nonhistone protein-DNA complexes Mol Cell 12 1525 1536 14690605
- Ivessa AS Zhou JQ Zakian VA 2000 The Saccharomyces Pif1p DNA helicase and the highly related Rrm3p have opposite effects on replication fork progression in ribosomal DNA Cell 100 479 489 10693764
- Lea DE Coulson CA 1949 The distribution of the numbers of mutants in bacterial populations J Genet 49 264 285 24536673
- Lipps HJ Rhodes D 2009 G-quadruplex structures: in vivo evidence and function Trends Cell Biol 19 414 422 19589679
- London TB Barber LJ Mosedale G Kelly GP Balasubramanian S Hickson ID Boulton SJ Hiom K 2008 FANCJ is a structure-specific DNA helicase associated with the maintenance of genomic G/C tracts J Biol Chem 283 36132 36139 18978354 PMC2662291
- Mateyak M Zakian V 2006 Human PIF helicase is cell cycle regulated and associates with telomerase Cell Cycle 23 2796 2804 17172855
- Myung K Chen C Kolodner RD 2001 Multiple pathways cooperate in the suppression of genome instability in Saccharomyces cerevisiae Nature 411 1073 1076 11429610
- Nakken S Rognes T Hovig E 2009 The disruptive positions in human G-quadruplex motifs are less polymorphic and more conserved than their neutral counterparts Nucleic Acids Res 37 5749 5756 19617376 PMC2761265
- Paeschke K McDonald KR Zakian VA 2010 Telomeres: Structures in need of unwinding FEBS letter 584 3769 3772 PMC2954063 20637196
- Ribeyre C Lopes J Boulé J Piazza P Guédin A Zakian V Mergny JL Nicolas A 2009 The yeast Pif1 helicase prevents genomic instability caused by G-quadruplex-forming CEB1 sequences in vivo PLoS Genet 5 e1000475 19424434 PMC2673046
- Runge KW Zakian VA 1989 Introduction of extra telomeric DNA sequences into Saccharomyces cerevisiae results in telomere elongation Mol Cell Biol 9 1488 1497 2657397 PMC362565
- Sanders CM 2010 Human Pif1 helicase is a G-quadruplex DNA binding protein with G-quadruplex DNA unwinding activity Biochem J 20524933
- Schulz VP Zakian VA 1994 The Saccharomyces PIF1 DNA helicase inhibits telomere elongation and de novo telomere formation Cell 76 145 155 8287473
- Sikorski RS Hieter P 1989 A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae Genetics 122 19 27 2659436 PMC1203683
- Storey JD 2003 The positive false discovery rate: A Bayesian interpretation and the q-value Annals of Statistics 31 2013 2035
- Vega L Phillips J BRT DPT Onigbanjo M Zakian V 2007 Sensitivity of yeast strains with long G-tails to levels of telomere-bound telomerase PLoS Genet 3 1065 1075 PMC1892048 17590086
- Yamagata K Kato J Shimamoto A Goto M Furuichi Y Ikeda H 1998 Bloom’s and Werner’s syndrome genes suppress hyperrecombination in yeast sgs1 mutant: implication for genomic instability in human diseases Proc Natl Acad Sci USA 95 8733 8738 9671747 PMC21145
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Sorted by citations
Quantitative visualization of DNA G-quadruplex structures in human cells
Biffi, G., Tannahill, D., McCafferty, J., & Balasubramanian, S. (2013) · Nature Chemistry · doi:10.1038/nchem.1548 · Cited by 2,152 · see citing works
DNA secondary structures: stability and function of G-quadruplex structures
Bochman, M. L., Paeschke, K., & Zakian, V. A. (2012) · Nature Reviews Genetics · doi:10.1038/nrg3296 · Cited by 1,449 · see citing works
Self-citationG-quadruplexes and their regulatory roles in biology
Rhodes, D., & Lipps, H. J. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv862 · Cited by 1,494 · see citing works
The regulation and functions of DNA and RNA G-quadruplexes
Varshney, D., Spiegel, J., Zyner, K. G., Tannahill, D., & Balasubramanian, S. (2020) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-020-0236-x · Cited by 1,265 · see citing works
R Loops: From Transcription Byproducts to Threats to Genome Stability
Aguilera, A., & García‐Muse, T. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.04.009 · Cited by 1,029 · see citing works
“These represent a strong barrier to DNA polymerases that requires the action of Pif1 helicase to allow RF progression (Lopes et al., 2011; Paeschke et al., 2011).”
BackgroundG-quadruplex structures mark human regulatory chromatin
Hänsel-Hertsch, R., Beraldi, D., Lensing, S. V., Marsico, G., Zyner, K., Parry, A., Di Antonio, M., Pike, J., Kimura, H., Narita, M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3662 · Cited by 964 · see citing works
The Structure and Function of DNA G-Quadruplexes
Spiegel, J., Adhikari, S., & Balasubramanian, S. (2020) · Trends in Chemistry · doi:10.1016/j.trechm.2019.07.002 · Cited by 920 · see citing works
“for a-thalassemia mental retardation X-linked (ATR-X) [53] and for the XPB and XPD helicases [54], yeast telomere binding protein RAP1-interacting factor 1 (Rif) [55], and yeast PIF1 helicase [56].”
BackgroundSmall-molecule–induced DNA damage identifies alternative DNA structures in human genes
Rodriguez, R., Miller, K. M., Forment, J. V., Bradshaw, C. R., Nikan, M., Britton, S., Oelschlaegel, T., Xhemalce, B., Balasubramanian, S., & Jackson, S. P. (2012) · Nature Chemical Biology · doi:10.1038/nchembio.780 · Cited by 741 · see citing works
“Genome-wide analyses have revealed a correlation of Pif1 binding to genomic sequences containing PQSs and to highly transcribed genes, suggesting that Pif1 may also regulate transcriptio”
Re-evaluation of G-quadruplex propensity with G4Hunter
Bedrat, A., Lacroix, L., & Mergny, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw006 · Cited by 693 · see citing works
DNA G-quadruplexes in the human genome: detection, functions and therapeutic potential
Hänsel‐Hertsch, R., Antonio, M. D., & Balasubramanian, S. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.3 · Cited by 882 · see citing works
Aguilera, A., & García-Muse, T. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-111212-133232 · Cited by 476 · see citing works
“In pif1 cells, replication slows down at regions that bear the G4 signature motif (152).”
BackgroundMaizels, N., & Graybuck, L. T. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003468 · Cited by 490 · see citing works
Pif1 family helicases suppress genome instability at G-quadruplex motifs
Paeschke, K., Bochman, M. L., Garcia, P. D., Ćejka, P., Friedman, K. L., Kowalczykowski, S. C., & Zakian, V. A. (2013) · Nature · doi:10.1038/nature12149 · Cited by 471 · see citing works
Self-citationG-quadruplexes: a promising target for cancer therapy
Kosiol, N., Juranek, S., Brossart, P., Heine, A., & Paeschke, K. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01328-4 · Cited by 540 · see citing works
“In general, G4 structure formation, if not regulated efficiently (this includes formation and unfolding), can stimulate genome instability, which includes muations and deletions and complex gross chromosomal rearrangements [28, 30, 220].”
BackgroundSelf-citationMendoza, Ó., Bourdoncle, A., Boulé, J.-B., Brosh, R. M., & Mergny, J. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw079 · Cited by 452 · see citing works
“Pif1 was originally thought to be a general guardian of double-stranded breaks through its inhibition of telomerase binding, but these recent experiments indicate that Pif1 also prevents deleterious events that lead to DNA breakage through its processing of G-rich secondary structures during or after replication (53,5…”
BackgroundTranscription–replication conflicts: how they occur and how they are resolved
García‐Muse, T., & Aguilera, A. (2016) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2016.88 · Cited by 417 · see citing works
Chromosome Duplication in Saccharomyces cerevisiae
Bell, S. P., & Labib, K. P. M. (2016) · Genetics · doi:10.1534/genetics.115.186452 · Cited by 352 · see citing works
DNA helicases involved in DNA repair and their roles in cancer
Brosh, R. M. (2013) · Nature reviews. Cancer · doi:10.1038/nrc3560 · Cited by 345 · see citing works
Everything You Ever Wanted to Know About Saccharomyces cerevisiae Telomeres: Beginning to End
Wellinger, R. J., & Zakian, V. A. (2012) · Genetics · doi:10.1534/genetics.111.137851 · Cited by 346 · see citing works
“This difficulty is thought to arise from the GC-rich nature of telomeric DNA, which gives it a high thermal stability and also allows it to form stable secondary structures, such as G-quadruplex DNA, which can pose problems for DNA replication (Lopes et al. 2011; Paeschke et al. 2011).”
BackgroundSelf-citationExistence and consequences of G-quadruplex structures in DNA
Murat, P., & Balasubramanian, S. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.10.012 · Cited by 346 · see citing works
Mechanisms and Regulation of Mitotic Recombination in Saccharomyces cerevisiae
Symington, L., Rothstein, R., & Lisby, M. (2014) · Genetics · doi:10.1534/genetics.114.166140 · Cited by 331 · see citing works
“Pif1 unwinds G4 structures in vitro and prevents replication fork stalling and DNA breakage at G4 motifs in vivo (Paeschke et al. 2011), which likely explains its suppression of recombination triggered by G-quadruplex forming tandem repeats (Ribeyre et al.”
BackgroundG‐quadruplex‐induced instability during leading‐strand replication
Lopes, J., Piazza, A., Bermejo, R., Kriegsman, B. A., Colosio, A., Teulade‐Fichou, M., Foiani, M., & Nicolas, A. G. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.316 · Cited by 330 · see citing works
“Here, complementary to the Paeschke et al (2011) study, we took advantage of the clearest demonstration that the minisatellite CEB1 can form G-quadruplex in S. cerevisiae cells (Ribeyre et al, 2009; Piazza et al, 2010) and specifically address whether G-quadruplexes affect replication and, if they…”
BackgroundInfluentialG-Quadruplexes: Prediction, Characterization, and Biological Application
Kwok, C. K., & Merrick, C. J. (2017) · Trends in biotechnology · doi:10.1016/j.tibtech.2017.06.012 · Cited by 393 · see citing works
“At a molecular level, ChIP has demonstrated that these helicases tend to associate with PQSs in the genome, particularly when cells are treated with G-quadruplex-stabilizing drugs [128], while in helicasedeficient cells, genes whose expression is deregulated likewise tend to contain PQSs [129].”
BackgroundPif1 helicase and Polδ promote recombination-coupled DNA synthesis via bubble migration
Wilson, M. A., Kwon, Y., Xu, Y., Chung, W., Chi, P., Niu, H.-Y., Mayle, R., Chen, X., Malkova, A., Sung, P., et al. (2013) · Nature · doi:10.1038/nature12585 · Cited by 313 · see citing works
Transcription as a source of genome instability
Kim, N., & Jinks-Robertson, S. (2012) · Nature reviews genetics · doi:10.1038/nrg3152 · Cited by 297 · see citing works
“In addition, ChIP–chip analysis has uncovered sequences that have G4-DNA-forming potential as preferential sites of yeast Pif1 association and as sites of replication slowin”
BackgroundMaizels, N. (2015) · EMBO Reports · doi:10.15252/embr.201540607 · Cited by 306 · see citing works
“The recent evidence that potentially unstable G4 motifs are dramatically depleted from the S. cerevisiae genome [19] has raised questions about a report claiming that the S. cerevisiae Pif1 helicase is enriched at G4 motifs and suppresses G4-induced genomic instability at those sites [34,35].”
Bulges in G-quadruplexes: broadening the definition of G-quadruplex-forming sequences.
Mukundan, V., & Phan, A. (2013) · Journal of the American Chemical Society · doi:10.1021/ja310251r · Cited by 274
Lago, S., Nadai, M., Cernilogar, F. M., Kazerani, M., Domíniguez Moreno, H., Schotta, G., & Richter, S. N. (2021) · Nature Communications · doi:10.1038/s41467-021-24198-2 · Cited by 269 · see citing works
Hänsel‐Hertsch, R., Spiegel, J., Marsico, G., Tannahill, D., & Balasubramanian, S. (2018) · Nature Protocols · doi:10.1038/nprot.2017.150 · Cited by 335 · see citing works
Recent Progress of Targeted G-Quadruplex-Preferred Ligands Toward Cancer Therapy
Asamitsu, S., Obata, S., Yu, Z., Bando, T., & Sugiyama, H. (2019) · Molecules · doi:10.3390/molecules24030429 · Cited by 276 · see citing works
Koole, W., van Schendel, R., Karambelas, A., van Heteren, J. V., Okihara, K. L., & Tijsterman, M. (2014) · Nature Communications · doi:10.1038/ncomms4216 · Cited by 230 · see citing works
Fluorescent Probes for G‐Quadruplex Structures
Vummidi, B. R., Alzeer, J., & Luedtke, N. W. (2013) · ChemBioChem · doi:10.1002/cbic.201200612 · Cited by 248 · see citing works
Landscape of G-quadruplex DNA structural regions in breast cancer
Hänsel-Hertsch, R., Simeone, A., Shea, A., Hui, W. W. I., Zyner, K. G., Marsico, G., Rueda, O. M., Bruna, A., Martin, A., Zhang, X., et al. (2020) · Nature Genetics · doi:10.1038/s41588-020-0672-8 · Cited by 223 · see citing works
G4 motifs affect origin positioning and efficiency in two vertebrate replicators
Valton, A.-L., Hassan‐Zadeh, V., Lema, I., Boggetto, N., Alberti, P., Saintomé, C., Riou, J., & Prioleau, M. (2014) · The EMBO Journal · doi:10.1002/embj.201387506 · Cited by 226 · see citing works
“…results of the SNS assay Recent studies have shown that in S. cerevisiae deletion of Pif1, a helicase known to unwind G4 structures, induces replication fork pausing at G4 mostly on the leading strand resulting in chromosomal breakages and rearrangements (Lopes et al , 2011; Paeschke et al , 2011).”
InfluentialInteraction of human telomeric DNA with N-methyl mesoporphyrin IX
Nicoludis, J. M., Barrett, S. P., Mergny, J., & Yatsunyk, L. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks152 · Cited by 208
“Data are being accumulated about in vivo existence of GQ structures (8–11) .”
G4Hunter web application: a web server for G-quadruplex prediction
Brázda, V., Kolomazník, J., Lýsek, J., Bartas, M., Fojta, M., Šťastný, J., & Mergny, J. (2019) · Bioinform. · doi:10.1093/bioinformatics/btz087 · Cited by 202 · see citing works
G‐quadruplexes: Emerging roles in neurodegenerative diseases and the non‐coding transcriptome
Simone, R., Fratta, P., Neidle, S., Parkinson, G. N., & Isaacs, A. M. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.05.003 · Cited by 216 · see citing works
“The Pif1 family of helicases, conserved from bacteria to humans, regulate DNA replication through G-quadruplexes, protecting the genome from DNA damage in the vicinity of these motifs, which are prone to breakage [30,31].”
BackgroundG quadruplexes are genomewide targets of transcriptional helicases XPB and XPD
Graybuck, L. T., Vallur, A. C., Eddy, J., & Maizels, N. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1475 · Cited by 211 · see citing works
“Genomewide associations of another G4 helicase, S. cerevisiae Pif1, were previously determined using a mutant derivative that lacked helicase activity in order to avoid that potential complication 42 .”
A non-canonical DNA structure is a binding motif for the transcription factor SP1 in vitro
Raiber, E., Kranaster, R., Lam, E. Y. N., Nikan, M., & Balasubramanian, S. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr882 · Cited by 232 · see citing works
Dynamic alternative DNA structures in biology and disease
Wang, G., & Vasquez, K. M. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-022-00539-9 · Cited by 196 · see citing works
Carr, A. M., & Lambert, S. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.04.023 · Cited by 179 · see citing works
Shivalingam, A., Izquierdo, M. A., Marois, A. L., Vyšniauskas, A., Suhling, K., Kuimova, M. K., & Vilar, R. (2015) · Nature Communications · doi:10.1038/ncomms9178 · Cited by 230 · see citing works
Wang, Y., Yang, J., Wild, A. T., Wu, W. H., Shah, R., Danussi, C., Riggins, G. J., Kannan, K., Sulman, E. P., Chan, T. A., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-08905-8 · Cited by 184 · see citing works
G-Quadruplex: A Regulator of Gene Expression and Its Chemical Targeting
Tian, T., Chen, Y., Wang, S., & Zhou, X. (2018) · Chem · doi:10.1016/j.chempr.2018.02.014 · Cited by 224 · see citing works
New insights into replication origin characteristics in metazoans
Cayrou, C., Coulombe, P., Puy, A., Rialle, S., Kaplan, N., Segal, E., & Méchali, M. (2012) · Cell Cycle · doi:10.4161/cc.11.4.19097 · Cited by 185 · see citing works
The chromatin environment shapes DNA replication origin organization and defines origin classesPreprint
Cayrou, C., Ballester, B., Peiffer, I., Fenouil, R., Coulombe, P., Andrau, J., van Helden, J., & Méchali, M. (2015) · Genome Research · doi:10.1101/gr.192799.115 · Cited by 199 · see citing works
“As G4 can inhibit replication fork progression (Sarkies et al. 2010; Paeschke et al. 2011), it could be asked how a replication inhibitory element might also stimulate replication.”
BackgroundG-quadruplex unwinding helicases and their function <i>in vivo</i>
Sauer, M., & Paeschke, K. (2017) · Biochemical Society Transactions · doi:10.1042/bst20170097 · Cited by 179 · see citing works
Self-citationDNA replication origins—where do we begin?Preprint
Prioleau, M., & MacAlpine, D. M. (2016) · Genes & Development · doi:10.1101/gad.285114.116 · Cited by 186 · see citing works
“The Pif1 helicase unwinds G4 structures, and loss of Pif1 results in replication fork stalling (Lopes et al. 2011; Paeschke et al. 2011) and genomic instability (Paeschke et al. 2013).”
BackgroundMammalian DNA2 helicase/nuclease cleaves G‐quadruplex DNA and is required for telomere integrity
Lin, W., Sampathi, S., Dai, H., Liu, C., Zhou, M., Hu, J., Huang, Q. M., Campbell, J. L., Shin‐ya, K., Zheng, L., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.88 · Cited by 166 · see citing works
“Taken together, these data suggest a positive correlation among DNA2 deficiency-induced telomere dysfunction, genome instabilities, and cancer development.”
G-Quadruplexes in DNA Replication: A Problem or a Necessity?
Valton, A.-L., & Prioleau, M.-N. (2016) · Trends in Genetics · doi:10.1016/j.tig.2016.09.004 · Cited by 149 · see citing works
Folding and misfolding pathways of G-quadruplex DNA
Marchand, A., & Gabélica, V. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw970 · Cited by 152 · see citing works
Impact of Alternative DNA Structures on DNA Damage, DNA Repair, and Genetic Instability
Wang, G., & Vasquez, K. M. (2014) · DNA Repair · doi:10.1016/j.dnarep.2014.03.017 · Cited by 152 · see citing works
FANCJ promotes DNA synthesis through G‐quadruplex structures
Bosch, P. C., Segura‐Bayona, S., Koole, W., Heteren, J. T. V., Dewar, J. M., Tijsterman, M., & Knipscheer, P. (2014) · The EMBO Journal · doi:10.15252/embj.201488663 · Cited by 154 · see citing works
“During DNA replication, ssDNA is present at the lagging strand template but also on the leading strand template in cases of transient uncoupling of the MCM helicase from the polymerase (Pacek & Walter, 2004).”
MethodFujimoto, T., Granzhan, A., Hänsel, R., Hurley, L., Kaiser, C., Moriyama, R., Spada, G., Sugimoto, N., Tran, P., Trantírek, L., et al. (2013) · doi:10.1007/978-3-642-34743-6 · Cited by 147
G-quadruplex formation in telomeres enhances POT1/TPP1 protection against RPA binding
Ray, S., Bandaria, J. N., Qureshi, M. H., Yıldız, A., & Balci, H. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1321436111 · Cited by 147 · see citing works
“Proc Natl Acad Sci USA 99(18):11593–11598.”
Ligand Design to Acquire Specificity to Intended G‐Quadruplex Structures
Asamitsu, S., Bando, T., & Sugiyama, H. (2018) · Chemistry - A European Journal · doi:10.1002/chem.201802691 · Cited by 165 · see citing works
The THO complex component Thp2 counteracts telomeric R‐loops and telomere shortening
Pfeiffer, V., Crittin, J., Grolimund, L., & Lingner, J. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.217 · Cited by 145 · see citing works
“This includes Rrm3 and Pif1 in Saccharomyces cerevisiae and Werner, RTEL1 and BLM in human cells (Ivessa et al , 2002; Crabbe et al , 2004; Sfeir et al , 2009; Paeschke et al , 2011; Vannier et al , 2012).”
Single-Molecule Analysis of mtDNA Replication Uncovers the Basis of the Common Deletion
Phillips, A. F., Millet, A. R., Tigano, M., Dubois, S. M., Crimmins, H., Babin, L., Charpentier, M., Piganeau, M., Brunet, E., & Sfeir, A. J. (2017) · Molecular Cell · doi:10.1016/j.molcel.2016.12.014 · Cited by 147 · see citing works
Replication of Telomeres and the Regulation of TelomerasePreprint
Pfeiffer, V., & Lingner, J. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a010405 · Cited by 137 · see citing works
“cerevisiae Pif1 is another DNA helicase important for replication of Grich sequences being enriched at telomeres and other G-rich sequences throughout the genome that may form G-quadruplex structures (Paeschke et al. 2011).”
BackgroundMüller, S., Sanders, D. A., Antonio, M. D., Matsis, S., Riou, J., Rodriguez, R., & Balasubramanian, S. (2012) · Organic & Biomolecular Chemistry · doi:10.1039/c2ob25830g · Cited by 147 · see citing works
G-quadruplex DNA: a novel target for drug design
Teng, F., Jiang, Z., Guo, M., Tan, X., Chen, F., Xi, X., & Xu, Y. (2021) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-021-03921-8 · Cited by 136 · see citing works
The chromatin remodeller ATRX: a repeat offender in human disease
Clynes, D., Higgs, D. R., & Gibbons, R. J. (2013) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2013.06.011 · Cited by 124 · see citing works
Structure of a left-handed DNA G-quadruplex
Chung, W. J., Heddi, B., Schmitt, E., Lim, K. W., Méchulam, Y., & Phan, A. T. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1418718112 · Cited by 148 · see citing works
“Recent studies demonstrated their existence in human cells (15) and their involvement in cellular regulation including recombination (12), replication (13, 14), transcription (10), and translation (11).”
BackgroundPiazza, A., Adrian, M., Samazan, F., Heddi, B., Hamon, F., Serero, A., Lopes, J., Teulade‐Fichou, M., Phan, A. T., & Nicolas, A. G. (2015) · The EMBO Journal · doi:10.15252/embj.201490702 · Cited by 142 · see citing works
“Differently, Capra et al , by relaxing the loop length constraint to 25 nt each, identified 552 and 446 potential G4 sequences in the S. cerevisiae (Capra et al , 2010; Paeschke et al , 2011) and S. pombe (Sabouri et al , 2014) genomes, respectively.”
Bharti, S. K., Sommers, J. A., George, F., Kuper, J., Hamon, F., Shin‐ya, K., Teulade‐Fichou, M., Kisker, C., & Brosh, R. M. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.m113.496463 · Cited by 136 · see citing works
“A role of Saccharomyces cerevisiae Pif1 to resolve G4 structures to preserve replication fork progression and suppress chromosomal breakage was determined (3).”
BackgroundZhang, S., Sun, H., Wang, L., Liu, Y., Chen, H., Li, Q., Guan, A., Liu, M., & Tang, Y. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky665 · Cited by 158 · see citing works
“G-quadruplex DNA, a non-canonical secondary nucleic acid structure formed by guanine-rich genomic sequences (1,2), has been viewed as an emerging therapeutic target in oncology due to its potential roles in oncogene transcriptional regulation (3), DNA replication (4) and telomere stability (5,6).”
BackgroundRetractedVisualizing the Quadruplex: From Fluorescent Ligands to Light-Up Probes
Largy, E., Granzhan, A., Hamon, F., Verga, D., & Teulade‐Fichou, M. (2012) · Topics in current chemistry · doi:10.1007/128_2012_346 · Cited by 130 · see citing works
G-quadruplex–R-loop interactions and the mechanism of anticancer G-quadruplex binders
Miglietta, G., Russo, M. V., & Capranico, G. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa944 · Cited by 135 · see citing works
“Pif1, and related family members, are among the most active helicases in resolving G4 structures and have been shown in yeast to prevent replication-dependent genetic and epigenetic alterations (131,132).”
BackgroundPIF1 family DNA helicases suppress R-loop mediated genome instability at tRNA genes
Tran, P. L. T., Pohl, T., Chen, C.-F., Chan, A., Pott, S., & Zakian, V. (2017) · Nature Communications · doi:10.1038/ncomms15025 · Cited by 121 · see citing works
“Here, * indicates P o 0.05, ** indicates P p 0.009, and **** indicates P o 0.0001. replication and suppresses DNA damage at G4 forming sequences 8,50–52 , as does Rrm3 in cells lacking Pif1 (ref.”
InfluentialSelf-citationStructural Basis of DNA Quadruplex–Duplex Junction Formation
Lim, K. W., & Phan, A. T. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201302995 · Cited by 128 · see citing works
RTEL1: functions of a disease-associated helicase
Vannier, J., Sarek, G., & Boulton, S. J. (2014) · Trends in Cell Biology · doi:10.1016/j.tcb.2014.01.004 · Cited by 134 · see citing works
Genomes and G-Quadruplexes: For Better or for Worse
Tarsounas, M., & Tijsterman, M. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.09.026 · Cited by 124 · see citing works
DSBCapture: in situ capture and sequencing of DNA breaks
Lensing, S. V., Marsico, G., Hänsel‐Hertsch, R., Lam, E. Y. N., Tannahill, D., & Balasubramanian, S. (2016) · Nature Methods · doi:10.1038/nmeth.3960 · Cited by 155 · see citing works
“G4 structures have been implicated as fragile sites during transcription and replication3,11,12, and have been associated with somatic copy number alterations in human cells13.”
Determinants of G quadruplex‐induced epigenetic instability in REV1‐deficient cells
Schiavone, D., Guilbaud, G., Murat, P., Papadopoulou, C., Sarkies, P., Prioleau, M., Balasubramanian, S., & Sale, J. E. (2014) · The EMBO Journal · doi:10.15252/embj.201488398 · Cited by 128 · see citing works
Association of G-quadruplex forming sequences with human mtDNA deletion breakpoints
Dong, D.-W. W., Pereira, F., Barrett, S. P., Kolesar, J., Cao, K.-J., Damas, J., Yatsunyk, L., Johnson, F., & Kaufman, B. A. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-677 · Cited by 116 · see citing works
“In addition, C secondary structure has an antiparallel component. lead to collapsed replication forks, similar to those observed in the nucleus near stabilized GQ sequences [48].”
Effect of loops and G-quartets on the stability of RNA G-quadruplexes.
Pandey, S., Agarwala, P., & Maiti, S. (2013) · Journal of Physical Chemistry B · doi:10.1021/jp401739m · Cited by 116 · see citing works
Guiblet, W. M., Cremona, M. A., Harris, R. S., Chen, D., Eckert, K. A., Chiaromonte, F., Huang, Y.-F., & Makova, K. D. (2021) · Nucleic Acids Research · doi:10.1093/nar/gkaa1269 · Cited by 115 · see citing works
G-quadruplex and i-motif are mutually exclusive in ILPR double-stranded DNA.
Dhakal, S., Yu, Z., Konik, R., Cui, Y.-X., Koirala, D., & Mao, H. (2012) · Biophysical Journal · doi:10.1016/j.bpj.2012.04.024 · Cited by 111
Zheng, K.-W., Xiao, S., Liu, J.-Q., Zhang, J.-Y., Hao, Y.-H., & Tan, Z. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt264 · Cited by 110
“This might be attributed to the presence of other factors in cells, like G-quadruplexresolving proteins (34), regulation at the translation level and other regulatory activities.”
BackgroundBiochemical Characterization of Warsaw Breakage Syndrome Helicase*
Wu, Y.-L., Sommers, J. A., Khan, I., de Winter, J., & Brosh, R. M. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.276022 · Cited by 110 · see citing works
“Pif1 was found to prevent genomic instability of aG-quadruplex (G4)(3) forming a human minisatellite sequence inserted into the Saccharomyces cerevisiae nuclear genome (9) and is involved in the DNA replication through G4 motifs (10) and coordination of checkpoint activation following telomere uncapping (11).”
BackgroundA quantitative telomeric chromatin isolation protocol identifies different telomeric states
Grolimund, L., Aeby, E., Hamelin, R., Armand, F., Chiappe, D., Moniatte, M., & Lingner, J. (2013) · Nature Communications · doi:10.1038/ncomms3848 · Cited by 115 · see citing works
Chow, T. T., Zhao, Y. B., Mak, S. S. M., Shay, J. W., & Wright, W. E. (2012) · Genes & Development · doi:10.1101/gad.187211.112 · Cited by 99 · see citing works
“…of the telomeric repeat and the ability to form G quartets make telomeres sensitive to fork stalling (Hao and Tan 2002; Lipps and Rhodes 2009; Paeschke et al. 2011), and a variety of proteins are required to allow replication of duplex telomeric DNA to proceed (Crabbe et al. 2004; Sfeir et…”
BackgroundBLM helicase suppresses recombination at G-quadruplex motifs in transcribed genes
van Wietmarschen, N., Merzouk, S., Halsema, N., Spierings, D. C. J., Guryev, V., & Lansdorp, P. M. (2018) · Nature Communications · doi:10.1038/s41467-017-02760-1 · Cited by 118 · see citing works
“…for DNA replication (Lopes et al., 2011) and previous studies have shown that specialized helicases such as Dog-1, Pif1 and FANCJ are required to prevent instability at G-rich genomic DNA in C.elegans (Cheung et al., 2002), yeast (Paeschke et al., 2011), and man (Castillo Bosch et al., 2014).”
BackgroundSabouri, N., McDonald, K. R., Webb, C. J., Cristea, I., & Zakian, V. (2012) · Genes & Development · doi:10.1101/gad.184697.111 · Cited by 108 · see citing works
“…fork progression at other sites where ScPif1 is not known to act, such as at tRNA genes, inactive origins, and the silent mating type loci, while ScPif1 is important for replication through G-rich motifs that can form G-quadruplex structures in vitro (Ivessa et al. 2003; Paeschke et al. 2011).”
BackgroundSelf-citationFormation of pearl-necklace monomorphic G-quadruplexes in the human CEB25 minisatellite.
Amrane, S., Adrian, M., Heddi, B., Serero, A., Nicolas, A., Mergny, J., & Phan, A. (2012) · Journal of the American Chemical Society · doi:10.1021/ja208993r · Cited by 107 · see citing works
ATRX Dysfunction Induces Replication Defects in Primary Mouse Cells
Clynes, D., Jelinska, C., Xella, B., Ayyub, H., Taylor, S., Mitson, M., Bachrati, C. Z., Higgs, D., & Gibbons, R. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092915 · Cited by 106 · see citing works
“Accumulating evidence suggests that the presence of such secondary structures serve as a barrier to replication fork progression, leading to fork stalling or collapse [26,27,28].”
BackgroundImpediments to replication fork movement: stabilisation, reactivation and genome instability
Lambert, S., & Carr, A. M. (2013) · Chromosoma · doi:10.1007/s00412-013-0398-9 · Cited by 98 · see citing works
G-quadruplex recognition and remodeling by the FANCJ helicase
Wu, C. G., & Spies, M. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw574 · Cited by 105 · see citing works
FANCJ couples replication past natural fork barriers with maintenance of chromatin structure
Schwab, R. A., Nieminuszczy, J., Shin‐ya, K., & Niedźwiedź, W. (2013) · The Journal of Cell Biology · doi:10.1083/jcb.201208009 · Cited by 102 · see citing works
“FANCJ is required to promote replication in the presence of the G4 stabilizer telomestatin Exposure to HU adversely affects survival of Pif1 mutant yeast cells by increasing fork stalling at G4 motifs (Paeschke et al., 2011).”
Mechanistic insight into the interaction of BLM helicase with intra-strand G-quadruplex structures
Chatterjee, S., Zagelbaum, J., Savitsky, P. A., Sturzenegger, A., Huttner, D., Janščák, P., Hickson, I. D., Gileadi, O., & Rothenberg, E. (2014) · Nature Communications · doi:10.1038/ncomms6556 · Cited by 102 · see citing works
“7a,b), WRN was able to unwind the G4 (10) but not the G4 substrate, whereas REQCL5 was unable to unwind either substrate (Supplementary Fig.”
BackgroundNon-duplex G-Quadruplex Structures Emerge as Mediators of Epigenetic Modifications
Mukherjee, A. K., Sharma, S., & Chowdhury, S. (2018) · Trends in Genetics · doi:10.1016/j.tig.2018.11.001 · Cited by 126 · see citing works
Overcoming natural replication barriers: differential helicase requirements
Anand, R., Shah, K., Niu, H., Sung, P., Mirkin, S. M., & Freudenreich, C. H. (2011) · Nucleic Acids Research · doi:10.1093/nar/gkr836 · Cited by 93 · see citing works
“More recently, it was shown to bind to a subset of G4 motifs in the yeast genome, and those motifs stimulated recombination and were more likely to mutate in a manner predicted to prevent G4 structure in pif1 mutants (18).”
BackgroundResultInfluentialAksenova, A. Y., & Mirkin, S. M. (2019) · Genes · doi:10.3390/genes10020118 · Cited by 110 · see citing works
Audry, J., Maestroni, L., Delagoutte, E., Gauthier, T., Nakamura, T., Gachet, Y., Saintomé, C., Géli, V., & Coulon, S. (2015) · The EMBO Journal · doi:10.15252/embj.201490773 · Cited by 92 · see citing works
“Given that one of the main function of scPif1 and hPIF1 is to remove G4 (Paeschke et al , 2011, 2013; Zhou et al , 2014), these results are consistent with our assumption that the D223Y mutation leads to accumulation of G4 at lagging telomeres during telomere replication either by preventing the…”
Dhakal, S., Cui, Y.-X., Koirala, D., Ghimire, C., Kushwaha, S., Yu, Z., Yangyuoru, P. M., & Mao, H. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt038 · Cited by 93
Charles, J. S., & Petes, T. D. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003434 · Cited by 99 · see citing works
“We also found a significant association between G-quadruplex motifs [21] and G1 conversion events, as well as an association between G-quadruplex motifs and conversion events initiated on the YJM789-derived chromosome; G-quadruplex structures slow replication fork progression [22].”
BackgroundDahan, D., Tsirkas, I., Dovrat, D., Sparks, M. A., Singh, S. P., Galletto, R., & Aharoni, A. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky1065 · Cited by 87 · see citing works
“Previously, G4(A) and G4(B) sequences derived from the yeast chromosomes IX and IV, respectively, were shown to generate G4 secondary structures in vitro (4), were identified as Pif1 binding sites in yeast and were shown to induce genome instability in yeast in the absence of Pif1 (12).”
BackgroundResultInfluentialBLM unfolds G-quadruplexes in different structural environments through different mechanisms
Wu, W., Hou, X.-M., Li, M., Dou, S.-X., & Xi, X.-G. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv361 · Cited by 90
“Although the isolated G4 has been recognized and studied in vitro by different biochemical and biophysical methods for more than three decades, the convincing evidences regarding G4 formation and regulation in cell by proteins have been recently confirmed by molecular probes and molecular genetic manipulations (18,19).”
BackgroundG-quadruplex formation in double strand DNA probed by NMM and CV fluorescence
Kreig, A., Calvert, J., Sanoica, J., Cullum, E., Tipanna, R., & Myong, S. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv749 · Cited by 89 · see citing works
Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae
Song, W., Dominska, M., Greenwell, P., & Petes, T. (2014) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.1406847111 · Cited by 88 · see citing works
“G-quadruplex sequences result in slowing of the replication fork in yeast (35, 36).”
Background
- Authors
- Paeschke, K., Capra, J. A., & Zakian, V. A.
- Affiliations
- Princeton University (US)
- Gladstone Institutes (US)
- Corresponding author
- Zakian, Virginia A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-05
- Volume
- 145
- Issue
- 5
- Pages
- 678-691
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3129610
- OpenAlex
- W1991754576
- Cited by
- 566
- References
- 51
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 34 · 2023: 31 · 2022: 27 · 2021: 48 · 2020: 38 · 2019: 38 · 2018: 36 · 2017: 38 · 2016: 53 · 2015: 39 · 2014: 45 · 2013: 54 · 2012: 33
- FWCI
- 18.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 844 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (R37GM026938, R01GM026938, GM-26938)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- G-quadruplex, DNA replication, Saccharomyces cerevisiae, replication fork stalling, DNA breakage, spontaneous mutation, replication stress
- MeSH terms
- DNA Polymerase II, DNA Replication, DNA Helicases, Saccharomyces cerevisiae, S Phase, Saccharomyces cerevisiae Proteins, G-Quadruplexes, DNA Copy Number Variations
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