{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T22:11:44Z","timestamp":1790633504858,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T00:00:00Z","timestamp":1584489600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Singapore Ministry of Education Academic Research Fund","award":["MOE2012-T3-1-001"],"award-info":[{"award-number":["MOE2012-T3-1-001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>G-quadruplexes are four-stranded nucleic acid structures involved in multiple cellular pathways including DNA replication and telomere maintenance. Such structures are formed by G-rich DNA sequences typified by telomeric DNA repeats. Whilst there is evidence for proteins that bind and regulate G-quadruplex formation, the molecular basis for this remains poorly understood. The budding yeast telomeric protein Rap1, originally identified as a transcriptional regulator functioning by recognizing double-stranded DNA binding sites, was one of the first proteins to be discovered to also bind and promote G-quadruplex formation in vitro. Here, we present the 2.4 \u00c5 resolution crystal structure of the Rap1 DNA-binding domain in complex with a G-quadruplex. Our structure not only provides a detailed insight into the structural basis for G-quadruplex recognition\u00a0by a protein, but also gives a mechanistic understanding of how the same DNA-binding domain adapts to specifically recognize different DNA structures. The key observation is the DNA-recognition helix functions in a bimodal manner: In double-stranded DNA recognition one helix face makes electrostatic interactions with the major groove of DNA, whereas in G-quadruplex recognition a different helix face is used to make primarily hydrophobic interactions with the planar face of a G-tetrad.<\/jats:p>","DOI":"10.1093\/nar\/gkaa171","type":"journal-article","created":{"date-parts":[[2020,3,15]],"date-time":"2020-03-15T12:30:12Z","timestamp":1584275412000},"page":"4562-4571","source":"Crossref","is-referenced-by-count":53,"title":["Structural basis of G-quadruplex DNA recognition by the yeast telomeric protein Rap1"],"prefix":"10.1093","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4018-8568","authenticated-orcid":false,"given":"Anna","family":"Traczyk","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive,\u00a0Singapore 637551, Singapore"},{"name":"NTU Institute of Structural Biology, Nanyang Technological University Singapore, 59 Nanyang Drive,\u00a0Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chong Wai","family":"Liew","sequence":"first","affiliation":[{"name":"NTU Institute of Structural Biology, Nanyang Technological University Singapore, 59 Nanyang Drive,\u00a0Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David James","family":"Gill","sequence":"first","affiliation":[{"name":"NTU Institute of Structural Biology, Nanyang Technological University Singapore, 59 Nanyang Drive,\u00a0Singapore 636921, Singapore"},{"name":"Lee Kong Chian School of Medicine, Nanyang Technological University Singapore, 59 Nanyang Drive,\u00a0Singapore 636921, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Rhodes","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Nanyang Technological University Singapore, 60 Nanyang Drive,\u00a0Singapore 637551, Singapore"},{"name":"NTU Institute of Structural Biology, Nanyang Technological University Singapore, 59 Nanyang Drive,\u00a0Singapore 636921, Singapore"},{"name":"School of Chemical and Biomedical Engineering, Nanyang Technological University Singapore, 62 Nanyang Drive,\u00a0Singapore 637459, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,3,18]]},"reference":[{"key":"2020043017193136100_B1","doi-asserted-by":"crossref","first-page":"8627","DOI":"10.1093\/nar\/gkv862","article-title":"G-quadruplexes and their regulatory roles in biology","volume":"43","author":"Rhodes","year":"2015","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B2","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1038\/nrg3296","article-title":"DNA secondary structures: stability and function of G-quadruplex structures","volume":"13","author":"Bochman","year":"2012","journal-title":"Nat. Rev. Genet."},{"key":"2020043017193136100_B3","doi-asserted-by":"crossref","first-page":"5402","DOI":"10.1093\/nar\/gkl655","article-title":"Quadruplex DNA: sequence, topology and structure","volume":"34","author":"Burge","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B4","doi-asserted-by":"crossref","first-page":"2901","DOI":"10.1093\/nar\/gki553","article-title":"Highly prevalent putative quadruplex sequence motifs in human DNA","volume":"33","author":"Todd","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B5","doi-asserted-by":"crossref","first-page":"2908","DOI":"10.1093\/nar\/gki609","article-title":"Prevalence of quadruplexes in the human genome","volume":"33","author":"Huppert","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B6","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1038\/nbt.3295","article-title":"High-throughput sequencing of DNA G-quadruplex structures in the human genome","volume":"33","author":"Chambers","year":"2015","journal-title":"Nat. Biotechnol."},{"key":"2020043017193136100_B7","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1371\/journal.pcbi.1000861","article-title":"G-quadruplex DNA sequences are evolutionarily conserved and associated with distinct genomic features in Saccharomyces cerevisiae","volume":"6","author":"Capra","year":"2010","journal-title":"PLoS Comput. Biol."},{"key":"2020043017193136100_B8","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.tcb.2009.05.002","article-title":"G-quadruplex structures: in vivo evidence and function","volume":"19","author":"Lipps","year":"2009","journal-title":"Trends Cell Biol."},{"key":"2020043017193136100_B9","doi-asserted-by":"crossref","first-page":"5987","DOI":"10.1021\/acs.jmedchem.5b01835","article-title":"Quadruplex nucleic acids as novel therapeutic targets","volume":"59","author":"Neidle","year":"2016","journal-title":"J. Med. Chem."},{"key":"2020043017193136100_B10","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.4155\/fmc-2015-0017","article-title":"Recent advances in targeting the telomeric G-quadruplex DNA sequence with small molecules as a strategy for anticancer therapies","volume":"8","author":"Islam","year":"2016","journal-title":"Future Med. Chem."},{"key":"2020043017193136100_B11","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1038\/nrm.2016.171","article-title":"Telomeres in cancer: tumour suppression and genome instability","volume":"18","author":"Maciejowski","year":"2017","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"2020043017193136100_B12","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1534\/genetics.111.137851","article-title":"Everything you ever wanted to know about Saccharomyces cerevisiae telomeres: beginning to end","volume":"191","author":"Wellinger","year":"2012","journal-title":"Genetics"},{"key":"2020043017193136100_B13","first-page":"378","article-title":"Telomeres","volume":"16","author":"Blackburn","year":"1991","journal-title":"Elsevier Science"},{"key":"2020043017193136100_B14","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1038\/342825a0","article-title":"Telomeric DNA dimerizes by formation of guanine tetrads between hairpin loops","volume":"342","author":"Sundquist","year":"1989","journal-title":"Nature"},{"key":"2020043017193136100_B15","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/0092-8674(89)90610-7","article-title":"Monovalent cation-induced structure of telomeric DNA: The G-quartet model","volume":"59","author":"Williamson","year":"1989","journal-title":"Cell"},{"key":"2020043017193136100_B16","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1038\/344410a0","article-title":"A sodium-potassium switch in the formation of four-stranded G4-DNA","volume":"344","author":"Sen","year":"1990","journal-title":"Nature"},{"key":"2020043017193136100_B17","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0092-8674(82)90109-X","article-title":"Cloning yeast telomeres on linear plasmid vectors","volume":"29","author":"Szostak","year":"1982","journal-title":"Cell"},{"key":"2020043017193136100_B18","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1002\/j.1460-2075.1994.tb06526.x","article-title":"The yeast telomere-binding protein RAP1 binds to and promotes the formation of DNA quadruplexes in telomeric DNA","volume":"13","author":"Giraldo","year":"1994","journal-title":"EMBO J."},{"key":"2020043017193136100_B19","doi-asserted-by":"crossref","first-page":"875","DOI":"10.1016\/0092-8674(93)90467-5","article-title":"The beta subunit of Oxytricha telomere-binding protein promotes G-quartet formation by telomeric DNA","volume":"74","author":"Fang","year":"1993","journal-title":"Cell"},{"key":"2020043017193136100_B20","doi-asserted-by":"crossref","first-page":"11646","DOI":"10.1021\/bi00094a022","article-title":"Characterization of a G-quartet formation reaction promoted by the \u03b2-subunit of the oxytricha telomere-binding protein","volume":"32","author":"Fang","year":"1993","journal-title":"Biochemistry"},{"key":"2020043017193136100_B21","doi-asserted-by":"crossref","first-page":"8572","DOI":"10.1073\/pnas.141229498","article-title":"In vitro generated antibodies specific for telomeric guanine-quadruplex DNA react with Stylonychia lemnae macronuclei","volume":"98","author":"Schaffitzel","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2020043017193136100_B22","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1038\/nsmb982","article-title":"Telomere end-binding proteins control the formation of G-quadruplex DNA structures in vivo","volume":"12","author":"Paeschke","year":"2005","journal-title":"Nat. Struct. Mol. Biol."},{"key":"2020043017193136100_B23","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1126\/science.2237406","article-title":"Involvement of the silencer and UAS binding protein RAP1 in regulation of telomere length","volume":"250","author":"Lustig","year":"1990","journal-title":"Science"},{"key":"2020043017193136100_B24","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1016\/0092-8674(87)90095-X","article-title":"Purification and cloning of a DNA binding protein from yeast that binds to both silencer and activator elements","volume":"51","author":"Shore","year":"1987","journal-title":"Cell"},{"key":"2020043017193136100_B25","doi-asserted-by":"crossref","first-page":"739","DOI":"10.1016\/0092-8674(90)90140-A","article-title":"RAP1 protein interacts with yeast telomeres in vivo: Overproduction alters telomere structure and decreases chromosome stability","volume":"63","author":"Conrad","year":"1990","journal-title":"Cell"},{"key":"2020043017193136100_B26","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.tibs.2009.08.006","article-title":"Plasticity of telomere maintenance mechanisms in yeast","volume":"35","author":"Lue","year":"2010","journal-title":"Trends Biochem. Sci."},{"key":"2020043017193136100_B27","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.1101\/gad.7.7a.1146","article-title":"RAP1 and telomere structure regulate telomere position effects in Saccharomyces cerevisiae","volume":"7","author":"Kyrion","year":"1993","journal-title":"Genes Dev."},{"key":"2020043017193136100_B28","doi-asserted-by":"crossref","first-page":"7481","DOI":"10.1128\/MCB.19.11.7481","article-title":"In vivo analysis of functional regions within yeast Rap1p","volume":"19","author":"Graham","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"2020043017193136100_B29","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0092-8674(00)81088-0","article-title":"The crystal structure of the DNA-binding domain of yeast RAP1 in complex with telomeric DNA","volume":"85","author":"Konig","year":"1996","journal-title":"Cell"},{"key":"2020043017193136100_B30","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1038\/sj.embor.7400314","article-title":"How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: a view from high-resolution crystal structures","volume":"6","author":"Court","year":"2005","journal-title":"EMBO Rep."},{"key":"2020043017193136100_B31","doi-asserted-by":"crossref","first-page":"7658","DOI":"10.1073\/pnas.91.16.7658","article-title":"Promotion of parallel DNA quadruplexes by a yeast telomere binding protein: a circular dichroism study","volume":"91","author":"Giraldo","year":"1994","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2020043017193136100_B32","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1107\/S0907444910048675","article-title":"iMOSFLM: A new graphical interface for diffraction-image processing with MOSFLM","volume":"67","author":"Battye","year":"2011","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2020043017193136100_B33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1107\/S0907444910045749","article-title":"Overview of the CCP 4 suite and current developments","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2020043017193136100_B34","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1107\/S0021889807021206","article-title":"Phaser crystallographic software","volume":"40","author":"McCoy","year":"2007","journal-title":"J. Appl. Crystallogr."},{"key":"2020043017193136100_B35","doi-asserted-by":"crossref","first-page":"14752","DOI":"10.1002\/chem.201103295","article-title":"Monomer-dimer equilibrium for the 5\u2032-5\u2032 stacking of propeller-type parallel-stranded g-quadruplexes: NMR structural study","volume":"18","author":"Do","year":"2012","journal-title":"Chem. - A Eur. J."},{"key":"2020043017193136100_B36","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1107\/S0907444911001314","article-title":"REFMAC5 for the refinement of macromolecular crystal structures","volume":"67","author":"Murshudov","year":"2011","journal-title":"Acta Crystallogr. Sect. D Biol. Crystallogr."},{"key":"2020043017193136100_B37","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1093\/nar\/gkm216","article-title":"MolProbity: All-atom contacts and structure validation for proteins and nucleic acids","volume":"35","author":"Davis","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B38","article-title":"The PyMOL Molecular Graphics System, Version 2.3","author":"Schr\u00f6dinger","year":"2015"},{"key":"2020043017193136100_B39","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1006\/jmbi.2000.4161","article-title":"How the multifunctional yeast Rap1p discriminates between DNA target sites: a crystallographic analysis","volume":"303","author":"Taylor","year":"2000","journal-title":"J. Mol. Biol."},{"key":"2020043017193136100_B40","doi-asserted-by":"crossref","first-page":"6219","DOI":"10.1093\/nar\/gkq372","article-title":"Role of the amino terminal RHAU-specific motif in the recognition and resolution of guanine quadruplex-RNA by the DEAH-box RNA helicase RHAU","volume":"38","author":"Lattmann","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2020043017193136100_B41","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/s41586-018-0209-9","article-title":"Structural basis of G-quadruplex unfolding by the DEAH\/RHA helicase DHX36","volume":"558","author":"Chen","year":"2018","journal-title":"Nature"},{"key":"2020043017193136100_B42","doi-asserted-by":"crossref","first-page":"2602","DOI":"10.1016\/j.bmcl.2014.04.029","article-title":"Small-molecule quadruplex-targeted drug discovery","volume":"24","author":"Ohnmacht","year":"2014","journal-title":"Bioorganic Med. Chem. Lett."},{"key":"2020043017193136100_B43","first-page":"201422605","article-title":"Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: solution structure of a peptide\u2013quadruplex complex","volume":"637371","author":"Heddi","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2020043017193136100_B44","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1126\/science.1147182","article-title":"Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends","volume":"318","author":"Azzalin","year":"2007","journal-title":"Science"}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/8\/4562\/33150685\/gkaa171.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/48\/8\/4562\/33150685\/gkaa171.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,4,30]],"date-time":"2020-04-30T21:22:27Z","timestamp":1588281747000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/48\/8\/4562\/5809672"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,18]]},"references-count":44,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2020,3,18]]},"published-print":{"date-parts":[[2020,5,7]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkaa171","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,5,7]]},"published":{"date-parts":[[2020,3,18]]}}}