{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T22:30:19Z","timestamp":1791412219362,"version":"4.3.3"},"reference-count":70,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T00:00:00Z","timestamp":1485216000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T00:00:00Z","timestamp":1485216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>DNA:RNA hybrids, nucleic acid structures with diverse physiological functions, can disrupt genome integrity when dysregulated. Human telomeres were shown to form hybrids with the lncRNA TERRA, yet the formation and distribution of these hybrids among telomeres, their regulation and their cellular effects remain elusive. Here we predict and confirm in several human cell types that DNA:RNA hybrids form at many subtelomeric and telomeric regions. We demonstrate that ICF syndrome cells, which exhibit short telomeres and elevated TERRA levels, are enriched for hybrids at telomeric regions throughout the cell cycle. Telomeric hybrids are associated with high levels of DNA damage at chromosome ends in ICF cells, which are significantly reduced with overexpression of RNase H1. Our findings suggest that abnormally high TERRA levels in ICF syndrome lead to accumulation of telomeric hybrids that, in turn, can result in telomeric dysfunction.<\/jats:p>","DOI":"10.1038\/ncomms14015","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T10:39:32Z","timestamp":1485254372000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":123,"title":["Telomeres in ICF syndrome cells are vulnerable to DNA damage due to elevated DNA:RNA hybrids"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-0256","authenticated-orcid":false,"given":"Shira","family":"Sagie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shir","family":"Toubiana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stella R.","family":"Hartono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hagar","family":"Katzir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aya","family":"Tzur-Gilat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shany","family":"Havazelet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Francastel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guillaume","family":"Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fr\u00e9d\u00e9ric","family":"Ch\u00e9din","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Selig","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,1,24]]},"reference":[{"key":"BFncomms14015_CR1","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s00412-006-0067-3","volume":"115","author":"N Hug","year":"2006","unstructured":"Hug, N. & Lingner, J. Telomere length homeostasis. Chromosoma 115, 413\u2013425 (2006).","journal-title":"Chromosoma"},{"key":"BFncomms14015_CR2","doi-asserted-by":"publisher","first-page":"48","DOI":"10.3389\/fonc.2013.00048","volume":"3","author":"MJ Giraud-Panis","year":"2013","unstructured":"Giraud-Panis, M. J. et al. One identity or more for telomeres? Front. Oncol. 3, 48 (2013).","journal-title":"Front. Oncol."},{"key":"BFncomms14015_CR3","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev.genet.41.110306.130350","volume":"42","author":"W Palm","year":"2008","unstructured":"Palm, W. & de Lange, T. How shelterin protects mammalian telomeres. Annu. Rev. Genet. 42, 301\u2013334 (2008).","journal-title":"Annu. Rev. Genet."},{"key":"BFncomms14015_CR4","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1006\/excr.1995.1213","volume":"219","author":"RC Allsopp","year":"1995","unstructured":"Allsopp, R. C. & Harley, C. B. Evidence for a critical telomere length in senescent human fibroblasts. Exp. Cell Res. 219, 130\u2013136 (1995).","journal-title":"Exp. Cell Res."},{"key":"BFncomms14015_CR5","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/S0092-8674(01)00504-9","volume":"107","author":"MT Hemann","year":"2001","unstructured":"Hemann, M. T., Strong, M. A., Hao, L. Y. & Greider, C. W. The shortest telomere, not average telomere length, is critical for cell viability and chromosome stability. Cell 107, 67\u201377 (2001).","journal-title":"Cell"},{"key":"BFncomms14015_CR6","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.1091\/mbc.e04-03-0207","volume":"15","author":"Y Zou","year":"2004","unstructured":"Zou, Y., Sfeir, A., Gryaznov, S. M., Shay, J. W. & Wright, W. E. Does a sentinel or a subset of short telomeres determine replicative senescence? Mol. Biol. Cell 15, 3709\u20133718 (2004).","journal-title":"Mol. Biol. Cell"},{"key":"BFncomms14015_CR7","doi-asserted-by":"publisher","first-page":"2186","DOI":"10.1261\/rna.1748309","volume":"15","author":"SG Nergadze","year":"2009","unstructured":"Nergadze, S. G. et al. CpG-island promoters drive transcription of human telomeres. RNA 15, 2186\u20132194 (2009).","journal-title":"RNA"},{"key":"BFncomms14015_CR8","doi-asserted-by":"publisher","first-page":"R151.151","DOI":"10.1186\/gb-2007-8-7-r151","volume":"8","author":"A Ambrosini","year":"2007","unstructured":"Ambrosini, A., Paul, S., Hu, S. & Riethman, H. Human subtelomeric duplicon structure and organization. Genome Biol. 8, R151.151\u2013R151.113 (2007).","journal-title":"Genome Biol."},{"key":"BFncomms14015_CR9","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fonc.2013.00046","volume":"3","author":"A Galati","year":"2013","unstructured":"Galati, A., Micheli, E. & Cacchione, S. Chromatin structure in telomere dynamics. Front. Oncol. 3, 46 (2013).","journal-title":"Front. Oncol."},{"key":"BFncomms14015_CR10","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1101\/gr.166983.113","volume":"24","author":"N Stong","year":"2014","unstructured":"Stong, N. et al. Subtelomeric CTCF and cohesin binding site organization using improved subtelomere assemblies and a novel annotation pipeline. Genome Res. 24, 1039\u20131050 (2014).","journal-title":"Genome Res."},{"key":"BFncomms14015_CR11","doi-asserted-by":"publisher","first-page":"798","DOI":"10.1126\/science.1147182","volume":"318","author":"CM Azzalin","year":"2007","unstructured":"Azzalin, C. M., Reichenback, P., Khoriauli, L., Giulotto, E. & Lingner, J. Telomeric repeat containing RNA and RNA surveillance factors at mammalian chromosome ends. Science 318, 798\u2013801 (2007).","journal-title":"Science"},{"key":"BFncomms14015_CR12","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1038\/ncb1685","volume":"10","author":"S Schoeftner","year":"2008","unstructured":"Schoeftner, S. & Blasco, M. A. Developmentally regulated transcription of mammalian telomeres by DNA-dependent RNA polymerase II. Nat. Cell Biol. 10, 228\u2013236 (2008).","journal-title":"Nat. Cell Biol."},{"key":"BFncomms14015_CR13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.tcb.2014.08.007","volume":"25","author":"CM Azzalin","year":"2014","unstructured":"Azzalin, C. M. & Lingner, J. Telomere functions grounding on TERRA firma. Trends Cell Biol. 25, 29\u201336 (2014).","journal-title":"Trends Cell Biol."},{"key":"BFncomms14015_CR14","doi-asserted-by":"publisher","first-page":"1199","DOI":"10.1038\/nsmb.2662","volume":"20","author":"B Balk","year":"2013","unstructured":"Balk, B. et al. Telomeric RNA-DNA hybrids affect telomere-length dynamics and senescence. Nat. Struct. Mol. Biol. 20, 1199\u201312052 (2013).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFncomms14015_CR15","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.molcel.2013.08.029","volume":"51","author":"E Cusanelli","year":"2013","unstructured":"Cusanelli, E., Romero, C. A. & Chartrand, P. Telomeric noncoding RNA TERRA is induced by telomere shortening to nucleate telomerase molecules at short telomeres. Mol. Cell 51, 780\u2013791 (2013).","journal-title":"Mol. Cell"},{"key":"BFncomms14015_CR16","doi-asserted-by":"publisher","first-page":"843","DOI":"10.4161\/rna.20330","volume":"9","author":"A Maicher","year":"2012","unstructured":"Maicher, A., Kastner, L. & Luke, B. Telomeres and disease: enter TERRA. RNA Biol. 9, 843\u2013849 (2012).","journal-title":"RNA Biol."},{"key":"BFncomms14015_CR17","doi-asserted-by":"publisher","first-page":"e1002747","DOI":"10.1371\/journal.pgen.1002747","volume":"8","author":"V Pfeiffer","year":"2012","unstructured":"Pfeiffer, V. & Lingner, J. TERRA promotes telomere shortening through exonuclease 1-mediated resection of chromosome ends. PLoS Genet. 8, e1002747 (2012).","journal-title":"PLoS Genet."},{"key":"BFncomms14015_CR18","doi-asserted-by":"publisher","first-page":"9117","DOI":"10.1093\/nar\/gkt695","volume":"41","author":"S Redon","year":"2013","unstructured":"Redon, S., Zemp, I. & Lingner, J. A three-state model for the regulation of telomerase by TERRA and hnRNPA1. Nucleic Acids Res. 41, 9117\u20139128 (2013).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms14015_CR19","doi-asserted-by":"publisher","first-page":"245","DOI":"10.3389\/fonc.2013.00245","volume":"3","author":"V Vitelli","year":"2013","unstructured":"Vitelli, V. et al. More on the lack of correlation between TERRA expression and telomere length. Front. Oncol. 3, 245 (2013).","journal-title":"Front. Oncol."},{"key":"BFncomms14015_CR20","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1038\/nsmb.3078","volume":"22","author":"K Rippe","year":"2015","unstructured":"Rippe, K. & Luke, B. TERRA and the state of the telomere. Nat. Struct. Mol. Biol. 22, 853\u2013858 (2015).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFncomms14015_CR21","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/nrg3961","volume":"16","author":"JM Santos-Pereira","year":"2015","unstructured":"Santos-Pereira, J. M. & Aguilera, A. R loops: new modulators of genome dynamics and function. Nat. Rev. Genet. 16, 583\u2013597 (2015).","journal-title":"Nat. Rev. Genet."},{"key":"BFncomms14015_CR22","doi-asserted-by":"publisher","first-page":"814","DOI":"10.1016\/j.molcel.2012.01.017","volume":"45","author":"PA Ginno","year":"2012","unstructured":"Ginno, P. A., Lott, P. L., Christensen, H. C., Korf, I. & Chedin, F. R-loop formation is a distinctive characteristic of unmethylated human CpG island promoters. Mol. Cell 45, 814\u2013825 (2012).","journal-title":"Mol. Cell"},{"key":"BFncomms14015_CR23","first-page":"9729","volume":"43","author":"SR Hartono","year":"2015","unstructured":"Hartono, S. R., Korf, I. F. & Chedin, F. GC skew is a conserved property of unmethylated CpG island promoters across vertebrates. Nucleic Acids Res. 43, 9729\u20139741 (2015).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms14015_CR24","doi-asserted-by":"publisher","first-page":"158","DOI":"10.3389\/fgene.2015.00158","volume":"6","author":"R Lombrana","year":"2015","unstructured":"Lombrana, R., Almeida, R., Alvarez, A. & Gomez, M. R-loops and initiation of DNA replication in human cells: a missing link? Front. Genet. 6, 158 (2015).","journal-title":"Front. Genet."},{"key":"BFncomms14015_CR25","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/ni919","volume":"4","author":"K Yu","year":"2003","unstructured":"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. 4, 442\u2013451 (2003).","journal-title":"Nat. Immunol."},{"key":"BFncomms14015_CR26","doi-asserted-by":"publisher","first-page":"2041","DOI":"10.1101\/gad.17010011","volume":"25","author":"W Gan","year":"2011","unstructured":"Gan, W. et al. R-loop-mediated genomic instability is caused by impairment of replication fork progression. Genes Dev. 25, 2041\u20132056 (2011).","journal-title":"Genes Dev."},{"key":"BFncomms14015_CR27","doi-asserted-by":"publisher","first-page":"e1004630","DOI":"10.1371\/journal.pgen.1004630","volume":"10","author":"M Groh","year":"2014","unstructured":"Groh, M. & Gromak, N. Out of balance: R-loops in human disease. PLoS Genet. 10, e1004630 (2014).","journal-title":"PLoS Genet."},{"key":"BFncomms14015_CR28","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1038\/emboj.2013.217","volume":"32","author":"V Pfeiffer","year":"2013","unstructured":"Pfeiffer, V., Crittin, J., Grolimund, L. & Lingner, J. The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening. EMBO J. 32, 2861\u20132871 (2013).","journal-title":"EMBO J."},{"key":"BFncomms14015_CR29","doi-asserted-by":"publisher","first-page":"3377","DOI":"10.1073\/pnas.1307415111","volume":"111","author":"TY Yu","year":"2014","unstructured":"Yu, T. Y., Kao, Y. W. & Lin, J. J. Telomeric transcripts stimulate telomere recombination to suppress senescence in cells lacking telomerase. Proc. Natl Acad. Sci. USA 111, 3377\u20133382 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14015_CR30","doi-asserted-by":"publisher","first-page":"5220","DOI":"10.1038\/ncomms6220","volume":"5","author":"R Arora","year":"2014","unstructured":"Arora, R. et al. RNaseH1 regulates TERRA-telomeric DNA hybrids and telomere maintenance in ALT tumour cells. Nat. Commun. 5, 5220 (2014).","journal-title":"Nat. Commun."},{"key":"BFncomms14015_CR31","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1038\/46052","volume":"402","author":"GL Xu","year":"1999","unstructured":"Xu, G. L. et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 402, 187\u2013191 (1999).","journal-title":"Nature"},{"key":"BFncomms14015_CR32","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1016\/S0092-8674(00)81656-6","volume":"99","author":"M Okano","year":"1999","unstructured":"Okano, M., Bell, D. W., Haber, D. A. & Li, E. DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247\u2013257 (1999).","journal-title":"Cell"},{"key":"BFncomms14015_CR33","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1093\/hmg\/ddn177","volume":"17","author":"S Yehezkel","year":"2008","unstructured":"Yehezkel, S., Segev, Y., Viegas-Pequignot, E., Skorecki, K. & Selig, S. Hypomethylation of subtelomeric regions in ICF syndrome is associated with abnormally short telomeres and enhanced transcription from telomeric regions. Hum. Mol. Genet. 17, 2776\u20132789 (2008).","journal-title":"Hum. Mol. Genet."},{"key":"BFncomms14015_CR34","doi-asserted-by":"publisher","first-page":"69","DOI":"10.4161\/cc.9.1.10358","volume":"9","author":"Z Deng","year":"2010","unstructured":"Deng, Z., Campbell, A. E. & Lieberman, P. M. TERRA, CpG methylation and telomere heterochromatin: lessons from ICF syndrome cells. Cell Cycle 9, 69\u201374 (2010).","journal-title":"Cell Cycle"},{"key":"BFncomms14015_CR35","doi-asserted-by":"publisher","first-page":"35","DOI":"10.3389\/fonc.2013.00035","volume":"3","author":"S Yehezkel","year":"2013","unstructured":"Yehezkel, S. et al. Characterization and rescue of telomeric abnormalities in ICF syndrome type I fibroblasts. Front. Oncol. 3, 35 (2013).","journal-title":"Front. Oncol."},{"key":"BFncomms14015_CR36","doi-asserted-by":"publisher","first-page":"2503","DOI":"10.1038\/emboj.2009.166","volume":"28","author":"B Luke","year":"2009","unstructured":"Luke, B. & Lingner, J. TERRA: telomeric repeat-containing RNA. EMBO J. 28, 2503\u20132510 (2009).","journal-title":"EMBO J."},{"key":"BFncomms14015_CR37","doi-asserted-by":"publisher","first-page":"3629","DOI":"10.1093\/hmg\/ddu071","volume":"23","author":"S Sagie","year":"2014","unstructured":"Sagie, S. et al. Induced pluripotent stem cells as a model for telomeric abnormalities in ICF type I syndrome. Hum. Mol. Genet. 23, 3629\u20133640 (2014).","journal-title":"Hum. Mol. Genet."},{"key":"BFncomms14015_CR38","doi-asserted-by":"publisher","first-page":"5379","DOI":"10.1038\/ncomms6379","volume":"5","author":"A Porro","year":"2014","unstructured":"Porro, A. et al. Functional characterization of the TERRA transcriptome at damaged telomeres. Nat. Commun. 5, 5379 (2014).","journal-title":"Nat. Commun."},{"key":"BFncomms14015_CR39","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1016\/j.molcel.2003.08.010","volume":"12","author":"P Huertas","year":"2003","unstructured":"Huertas, P. & Aguilera, A. Cotranscriptionally formed DNA:RNA hybrids mediate transcription elongation impairment and transcription-associated recombination. Mol. Cell 12, 711\u2013721 (2003).","journal-title":"Mol. Cell"},{"issue":"7","key":"BFncomms14015_CR40","doi-asserted-by":"publisher","first-page":"e1600031","DOI":"10.1126\/sciadv.1600031","volume":"2","author":"Aur\u00e9lie Diman","year":"2016","unstructured":"Diman, A. et al. Nuclear respiratory factor 1 and endurance exercise promote human telomere transcription. Sci. Adv. 2, (2016).","journal-title":"Science Advances"},{"key":"BFncomms14015_CR41","doi-asserted-by":"publisher","first-page":"1590","DOI":"10.1101\/gr.158436.113","volume":"23","author":"PA Ginno","year":"2013","unstructured":"Ginno, P. A., Lim, Y. W., Lott, P. L., Korf, I. & Chedin, F. GC skew at the 5\u2032 and 3\u2032 ends of human genes links R-loop formation to epigenetic regulation and transcription termination. Genome Res. 23, 1590\u20131600 (2013).","journal-title":"Genome Res."},{"key":"BFncomms14015_CR42","doi-asserted-by":"publisher","first-page":"e08007","DOI":"10.7554\/eLife.08007","volume":"4","author":"YW Lim","year":"2015","unstructured":"Lim, Y. W., Sanz, L. A., Xu, X., Hartono, S. R. & Chedin, F. Genome-wide DNA hypomethylation and RNA:DNA hybrid accumulation in Aicardi-Goutieres syndrome. eLife 4, e08007 (2015).","journal-title":"eLife"},{"key":"BFncomms14015_CR43","doi-asserted-by":"publisher","first-page":"e1004294","DOI":"10.1371\/journal.pgen.1004294","volume":"10","author":"EW Loomis","year":"2014","unstructured":"Loomis, E. W., Sanz, L. A., Chedin, F. & Hagerman, P. J. Transcription-associated R-loop formation across the human FMR1 CGG-repeat region. PLoS Genet. 10, e1004294 (2014).","journal-title":"PLoS Genet."},{"key":"BFncomms14015_CR44","doi-asserted-by":"publisher","first-page":"6649","DOI":"10.1093\/nar\/gks358","volume":"40","author":"A Maicher","year":"2012","unstructured":"Maicher, A., Kastner, L., Dees, M. & Luke, B. Deregulated telomere transcription causes replication-dependent telomere shortening and promotes cellular senescence. Nucleic Acids Res. 40, 6649\u20136659 (2012).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms14015_CR45","doi-asserted-by":"publisher","first-page":"4808","DOI":"10.1128\/MCB.00460-10","volume":"30","author":"A Porro","year":"2010","unstructured":"Porro, A., Feuerhahn, S., Reichenbach, P. & Lingner, J. Molecular dissection of telomeric repeat-containing RNA biogenesis unveils the presence of distinct and multiple regulatory pathways. Mol. Cell Biol. 30, 4808\u20134817 (2010).","journal-title":"Mol. Cell Biol."},{"key":"BFncomms14015_CR46","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1126\/science.1257216","volume":"347","author":"RL Flynn","year":"2015","unstructured":"Flynn, R. L. et al. Alternative lengthening of telomeres renders cancer cells hypersensitive to ATR inhibitors. Science 347, 273\u2013277 (2015).","journal-title":"Science"},{"key":"BFncomms14015_CR47","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1038\/nature09772","volume":"471","author":"RL Flynn","year":"2011","unstructured":"Flynn, R. L. et al. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 471, 532\u2013536 (2011).","journal-title":"Nature"},{"key":"BFncomms14015_CR48","doi-asserted-by":"publisher","first-page":"948","DOI":"10.1038\/nsmb.2364","volume":"19","author":"N Arnoult","year":"2012","unstructured":"Arnoult, N., Van Beneden, A. & Decottignies, A. Telomere length regulates TERRA levels through increased trimethylation of telomeric H3K9 and HP1alpha. Nat. Struct. Mol. Biol. 19, 948\u2013956 (2012).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFncomms14015_CR49","doi-asserted-by":"publisher","first-page":"166","DOI":"10.3389\/fgene.2015.00166","volume":"6","author":"A Brambati","year":"2015","unstructured":"Brambati, A., Colosio, A., Zardoni, L., Galanti, L. & Liberi, G. Replication and transcription on a collision course: eukaryotic regulation mechanisms and implications for DNA stability. Front. Genet. 6, 166 (2015).","journal-title":"Front. Genet."},{"key":"BFncomms14015_CR50","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.tcb.2015.05.003","volume":"25","author":"J Sollier","year":"2015","unstructured":"Sollier, J. & Cimprich, K. A. Breaking bad: R-loops and genome integrity. Trends Cell Biol. 25, 514\u2013522 (2015).","journal-title":"Trends Cell Biol."},{"key":"BFncomms14015_CR51","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1111\/j.1742-4658.2009.07464.x","volume":"277","author":"AT Phan","year":"2010","unstructured":"Phan, A. T. Human telomeric G-quadruplex: structures of DNA and RNA sequences. FEBS J. 277, 1107\u20131117 (2010).","journal-title":"FEBS J."},{"key":"BFncomms14015_CR52","doi-asserted-by":"publisher","first-page":"2995","DOI":"10.1093\/nar\/gkr1153","volume":"40","author":"A Bah","year":"2012","unstructured":"Bah, A., Wischnewski, H., Shchepachev, V. & Azzalin, C. M. The telomeric transcriptome of Schizosaccharomyces pombe. Nucleic Acids Res. 40, 2995\u20133005 (2012).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms14015_CR53","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/nsmb.2543","volume":"20","author":"A Helmrich","year":"2013","unstructured":"Helmrich, A., Ballarino, M., Nudler, E. & Tora, L. Transcription-replication encounters, consequences and genomic instability. Nat. Struct. Mol. Biol. 20, 412\u2013418 (2013).","journal-title":"Nat. Struct. Mol. Biol."},{"key":"BFncomms14015_CR54","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3389\/fgene.2015.00143","volume":"6","author":"E Cusanelli","year":"2015","unstructured":"Cusanelli, E. & Chartrand, P. Telomeric repeat-containing RNA TERRA: a noncoding RNA connecting telomere biology to genome integrity. Front. Genet. 6, 143 (2015).","journal-title":"Front. Genet."},{"key":"BFncomms14015_CR55","doi-asserted-by":"publisher","first-page":"877","DOI":"10.2217\/epi.15.55","volume":"7","author":"S Lalevee","year":"2015","unstructured":"Lalevee, S. & Feil, R. Long noncoding RNAs in human disease: emerging mechanisms and therapeutic strategies. Epigenomics 7, 877\u2013879 (2015).","journal-title":"Epigenomics"},{"key":"BFncomms14015_CR56","doi-asserted-by":"publisher","first-page":"4391","DOI":"10.1093\/nar\/gku114","volume":"42","author":"H Episkopou","year":"2014","unstructured":"Episkopou, H. et al. Alternative lengthening of telomeres is characterized by reduced compaction of telomeric chromatin. Nucleic Acids Res. 42, 4391\u20134405 (2014).","journal-title":"Nucleic Acids Res."},{"key":"BFncomms14015_CR57","doi-asserted-by":"publisher","first-page":"6817","DOI":"10.1038\/onc.2008.289","volume":"27","author":"E Vera","year":"2008","unstructured":"Vera, E., Canela, A., Fraga, M. F., Esteller, M. & Blasco, M. A. Epigenetic regulation of telomeres in human cancer. Oncogene 27, 6817\u20136833 (2008).","journal-title":"Oncogene"},{"key":"BFncomms14015_CR58","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1038\/onc.2009.23","volume":"28","author":"G Tilman","year":"2009","unstructured":"Tilman, G. et al. Subtelomeric DNA hypomethylation is not required for telomeric sister chromatid exchanges in ALT cells. Oncogene 28, 1682\u20131693 (2009).","journal-title":"Oncogene"},{"key":"BFncomms14015_CR59","doi-asserted-by":"publisher","first-page":"82","DOI":"10.1016\/j.canlet.2009.02.031","volume":"281","author":"ME Lee","year":"2009","unstructured":"Lee, M. E., Rha, S. Y., Jeung, H. C., Chung, H. C. & Oh, B. K. Subtelomeric DNA methylation and telomere length in human cancer cells. Cancer Lett. 281, 82\u201391 (2009).","journal-title":"Cancer Lett."},{"key":"BFncomms14015_CR60","doi-asserted-by":"publisher","first-page":"7538","DOI":"10.1038\/ncomms8538","volume":"6","author":"D Clynes","year":"2015","unstructured":"Clynes, D. et al. Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX. Nat. Commun. 6, 7538 (2015).","journal-title":"Nat. Commun."},{"key":"BFncomms14015_CR61","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1186\/1750-1172-9-56","volume":"9","author":"G Velasco","year":"2014","unstructured":"Velasco, G. et al. Germline genes hypomethylation and expression define a molecular signature in peripheral blood of ICF patients: implications for diagnosis and etiology. Orphanet. J. Rare Dis. 9, 56 (2014).","journal-title":"Orphanet. J. Rare Dis."},{"key":"BFncomms14015_CR62","doi-asserted-by":"publisher","first-page":"11434","DOI":"10.1073\/pnas.96.20.11434","volume":"96","author":"R Ofir","year":"1999","unstructured":"Ofir, R., Wong, A. C., McDermid, H. E., Skorecki, K. L. & Selig, S. Position effect of human telomeric repeats on replication timing. Proc. Natl Acad. Sci. USA 96, 11434\u201311439 (1999).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14015_CR63","doi-asserted-by":"publisher","first-page":"6622","DOI":"10.1073\/pnas.85.18.6622","volume":"85","author":"RK Moyzis","year":"1988","unstructured":"Moyzis, R. K. et al. A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes. Proc. Natl Acad. Sci. USA 85, 6622\u20136626 (1988).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14015_CR64","doi-asserted-by":"publisher","first-page":"8861","DOI":"10.1073\/pnas.91.19.8861","volume":"91","author":"JP Hanish","year":"1994","unstructured":"Hanish, J. P., Yanowitz, J. L. & de Lange, T. Stringent sequence requirements for the formation of human telomeres. Proc. Natl Acad. Sci. USA 91, 8861\u20138865 (1994).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"BFncomms14015_CR65","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/S1097-2765(03)00088-1","volume":"11","author":"SM Cerritelli","year":"2003","unstructured":"Cerritelli, S. M. et al. Failure to produce mitochondrial DNA results in embryonic lethality in Rnaseh1 null mice. Mol. Cell 11, 807\u2013815 (2003).","journal-title":"Mol. Cell"},{"key":"BFncomms14015_CR66","unstructured":"Aronesty, E. Command-line tools for processing biological sequencing data. https:\/\/github.com\/ExpressionAnalysis\/ea-utils (2011)."},{"key":"BFncomms14015_CR67","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/nmeth.1923","volume":"9","author":"B Langmead","year":"2012","unstructured":"Langmead, B. & Salzberg, S. L. Fast gapped-read alignment with Bowtie 2. Nat. Methods 9, 357\u2013359 (2012).","journal-title":"Nat. Methods"},{"key":"BFncomms14015_CR68","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25, 2078\u20132079 (2009).","journal-title":"Bioinformatics"},{"key":"BFncomms14015_CR69","doi-asserted-by":"publisher","first-page":"R137","DOI":"10.1186\/gb-2008-9-9-r137","volume":"9","author":"Y Zhang","year":"2008","unstructured":"Zhang, Y. et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol. 9, R137 (2008).","journal-title":"Genome Biol."},{"key":"BFncomms14015_CR70","doi-asserted-by":"publisher","first-page":"1244","DOI":"10.1038\/nsmb.1725","volume":"16","author":"AJ Cesare","year":"2009","unstructured":"Cesare, A. J. et al. Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nat. Struct. Mol. Biol. 16, 1244\u20131251 (2009).","journal-title":"Nat. Struct. Mol. Biol."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/ncomms14015.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms14015","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/ncomms14015.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T23:52:22Z","timestamp":1671753142000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncomms14015"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,24]]},"references-count":70,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,4,28]]}},"alternative-id":["BFncomms14015"],"URL":"https:\/\/doi.org\/10.1038\/ncomms14015","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,24]]},"assertion":[{"value":"14 July 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 November 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 January 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"14015"}}