{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:29:10Z","timestamp":1787009350890,"version":"build-2736575974"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2020R1A2C3003352"],"award-info":[{"award-number":["2020R1A2C3003352"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2019R1A6A1A10073437"],"award-info":[{"award-number":["2019R1A6A1A10073437"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"MEST","doi-asserted-by":"publisher","award":["2020R1C1C101220611"],"award-info":[{"award-number":["2020R1C1C101220611"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002551","name":"Seoul National University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002551","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,4,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Karyotype change and subsequent evolution is triggered by chromosome fusion and rearrangement events, which often occur when telomeres become dysfunctional. Telomeres protect linear chromosome ends from DNA damage responses (DDRs), and telomere dysfunction may result in genome instability. However, the complex chromosome end structures and the other possible consequences of telomere dysfunction have rarely been resolved at the nucleotide level due to the lack of the high-throughput methods needed to analyse these highly repetitive regions. Here we applied long-read sequencing technology to Caenorhabditis elegans survivor lines that emerged after telomere dysfunction. The survivors have preserved traces of DDRs in their genomes and our data revealed that variants generated by telomere dysfunction are accumulated along all chromosomes. The reconstruction of the chromosome end structures through de novo genome assemblies revealed diverse types of telomere damage processing at the nucleotide level. When telomeric repeats were totally eroded by telomere dysfunction, DDRs were mostly terminated by chromosome fusion events. We also partially reconstructed the most complex end structure and its DDR signatures, which would have been accumulated via multiple cell divisions. These finely resolved chromosome end structures suggest possible mechanisms regarding the repair processes after telomere dysfunction, providing insights into chromosome evolution in nature.<\/jats:p>","DOI":"10.1093\/nar\/gkab141","type":"journal-article","created":{"date-parts":[[2021,2,20]],"date-time":"2021-02-20T15:11:16Z","timestamp":1613833876000},"page":"3338-3353","source":"Crossref","is-referenced-by-count":23,"title":["Long-read sequencing and\n                    <i>de novo<\/i>\n                    genome assemblies reveal complex chromosome end structures caused by telomere dysfunction at the single nucleotide level"],"prefix":"10.1093","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9425-6992","authenticated-orcid":false,"given":"Eunkyeong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul\u00a008826, Korea"},{"name":"Institute of Molecular Biology and Genetics, Seoul National University, Seoul\u00a008826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9753-4778","authenticated-orcid":false,"given":"Jun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul\u00a008826, Korea"},{"name":"Research Institute of Basic Sciences, Seoul National University, Seoul\u00a008826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2337-1106","authenticated-orcid":false,"given":"Chuna","family":"Kim","sequence":"additional","affiliation":[{"name":"Aging Research Center, Korea Research Institute of Bioscience and Biotechnology, Gwahak-ro 125, Daejeon\u00a034141, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6421-1195","authenticated-orcid":false,"given":"Junho","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Seoul National University, Gwanak-ro 1, Gwanak-gu, Seoul\u00a008826, Korea"},{"name":"Institute of Molecular Biology and Genetics, Seoul National University, Seoul\u00a008826, Korea"},{"name":"Research Institute of Basic Sciences, Seoul National University, Seoul\u00a008826, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,8]]},"reference":[{"key":"2021040616375822500_B1","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1534\/genetics.108.089920","article-title":"End joining at Caenorhabditis elegans telomeres","volume":"180","author":"Lowden","year":"2008","journal-title":"Genetics"},{"key":"2021040616375822500_B2","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1126\/science.1199022","article-title":"DNA synthesis generates terminal duplications that seal end-to-end chromosome fusions","volume":"332","author":"Lowden","year":"2011","journal-title":"Science"},{"key":"2021040616375822500_B3","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1038\/35020592","article-title":"Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice","volume":"406","author":"Artandi","year":"2000","journal-title":"Nature"},{"key":"2021040616375822500_B4","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/S0092-8674(01)00457-3","article-title":"Telomere dysfunction increases mutation rate and genomic instability","volume":"106","author":"Hackett","year":"2001","journal-title":"Cell"},{"key":"2021040616375822500_B5","doi-asserted-by":"crossref","first-page":"1900177","DOI":"10.1002\/bies.201900177","article-title":"Repair and reconstruction of telomeric and subtelomeric regions and genesis of new telomeres: implications for chromosome evolution","volume":"42","author":"Kim","year":"2020","journal-title":"Bioessays"},{"key":"2021040616375822500_B6","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1073\/pnas.25.8.405","article-title":"The behavior in successive nuclear divisions of a chromosome broken at meiosis","volume":"25","author":"McClintock","year":"1939","journal-title":"PNAS"},{"key":"2021040616375822500_B7","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1016\/S0959-8049(97)00062-2","article-title":"A survey of telomerase activity in human cancer","volume":"33","author":"Shay","year":"1997","journal-title":"Eur. J. Cancer"},{"key":"2021040616375822500_B8","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1128\/MCB.21.5.1819-1827.2001","article-title":"Two survivor pathways that allow growth in the absence of telomerase are generated by distinct telomere recombination events","volume":"21","author":"Chen","year":"2001","journal-title":"Mol. Cell. Biol."},{"key":"2021040616375822500_B9","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/nature20099","article-title":"Break-induced telomere synthesis underlies alternative telomere maintenance","volume":"539","author":"Dilley","year":"2016","journal-title":"Nature"},{"key":"2021040616375822500_B10","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/nm1197-1271","article-title":"Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines","volume":"3","author":"Bryan","year":"1997","journal-title":"Nat. Med."},{"key":"2021040616375822500_B11","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1007\/s00412-015-0528-7","article-title":"Telomerase lost?","volume":"125","author":"Mason","year":"2016","journal-title":"Chromosoma"},{"key":"2021040616375822500_B12","doi-asserted-by":"crossref","first-page":"8189","DOI":"10.1038\/ncomms9189","article-title":"Telomere maintenance through recruitment of internal genomic regions","volume":"6","author":"Seo","year":"2015","journal-title":"Nat. Commun."},{"key":"2021040616375822500_B13","first-page":"e1146856","volume-title":"Worm","author":"Kim","year":"2016"},{"key":"2021040616375822500_B14","doi-asserted-by":"crossref","first-page":"12683","DOI":"10.1073\/pnas.211357798","article-title":"Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors","volume":"98","author":"Gisselsson","year":"2001","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021040616375822500_B15","doi-asserted-by":"crossref","first-page":"2304","DOI":"10.1038\/sj.emboj.7600236","article-title":"Molecular analysis of telomere fusions in Arabidopsis: multiple pathways for chromosome end-joining","volume":"23","author":"Heacock","year":"2004","journal-title":"EMBO J."},{"key":"2021040616375822500_B16","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1038\/s41588-020-0667-5","article-title":"APOBEC3-dependent kataegis and TREX1-driven chromothripsis during telomere crisis","volume":"52","author":"Maciejowski","year":"2020","journal-title":"Nat. Genet."},{"key":"2021040616375822500_B17","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/nature05886","article-title":"Chromosomally unstable mouse tumours have genomic alterations similar to diverse human cancers","volume":"447","author":"Maser","year":"2007","journal-title":"Nature"},{"key":"2021040616375822500_B18","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1101\/gr.246082.118","article-title":"Long-read sequencing reveals intra-species tolerance of substantial structural variations and new subtelomere formation in C. elegans","volume":"29","author":"Kim","year":"2019","journal-title":"Genome Res."},{"key":"2021040616375822500_B19","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1101\/gr.244830.118","article-title":"Recompleting the Caenorhabditis elegans genome","volume":"29","author":"Yoshimura","year":"2019","journal-title":"Genome Res."},{"key":"2021040616375822500_B20","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1093\/nar\/29.1.82","article-title":"WormBase: network access to the genome and biology of Caenorhabditis elegans","volume":"29","author":"Stein","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"2021040616375822500_B21","first-page":"D762","article-title":"WormBase: a modern model organism information resource","volume":"48","author":"Harris","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"2021040616375822500_B22","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1101\/gr.215087.116","article-title":"Canu: scalable and accurate long-read assembly via adaptive k-mer weighting and repeat separation","volume":"27","author":"Koren","year":"2017","journal-title":"Genome Res."},{"key":"2021040616375822500_B23","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The sequence alignment\/map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"2021040616375822500_B24","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1101\/gr.214270.116","article-title":"Fast and accurate de novo genome assembly from long uncorrected reads","volume":"27","author":"Vaser","year":"2017","journal-title":"Genome Res."},{"key":"2021040616375822500_B25","doi-asserted-by":"crossref","first-page":"3210","DOI":"10.1093\/bioinformatics\/btv351","article-title":"BUSCO: assessing genome assembly and annotation completeness with single-copy orthologs","volume":"31","author":"Sim\u00e3o","year":"2015","journal-title":"Bioinformatics"},{"key":"2021040616375822500_B26","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1038\/s41592-018-0046-7","article-title":"Bioconda: sustainable and comprehensive software distribution for the life sciences","volume":"15","author":"Gr\u00fcning","year":"2018","journal-title":"Nat. Methods"},{"key":"2021040616375822500_B27","author":"Smit","year":"2015"},{"key":"2021040616375822500_B28","doi-asserted-by":"crossref","first-page":"D81","DOI":"10.1093\/nar\/gkv1272","article-title":"The Dfam database of repetitive DNA families","volume":"44","author":"Hubley","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"2021040616375822500_B29","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S0959-440X(98)80067-5","article-title":"Repeats in genomic DNA: mining and meaning","volume":"8","author":"Jurka","year":"1998","journal-title":"Curr. Opin. Struct. Biol."},{"key":"2021040616375822500_B30","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s13100-015-0041-9","article-title":"Repbase update, a database of repetitive elements in eukaryotic genomes","volume":"6","author":"Bao","year":"2015","journal-title":"Mobile Dna"},{"key":"2021040616375822500_B31","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/nar\/27.2.573","article-title":"Tandem repeats finder: a program to analyze DNA sequences","volume":"27","author":"Benson","year":"1999","journal-title":"Nucleic Acids Res."},{"key":"2021040616375822500_B32","doi-asserted-by":"crossref","first-page":"3094","DOI":"10.1093\/bioinformatics\/bty191","article-title":"Minimap2: pairwise alignment for nucleotide sequences","volume":"34","author":"Li","year":"2018","journal-title":"Bioinformatics"},{"key":"2021040616375822500_B33","doi-asserted-by":"crossref","first-page":"e1005944","DOI":"10.1371\/journal.pcbi.1005944","article-title":"MUMmer4: a fast and versatile genome alignment system","volume":"14","author":"Mar\u00e7ais","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"2021040616375822500_B34","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/bioinformatics\/btw369","article-title":"Assemblytics: a web analytics tool for the detection of variants from an assembly","volume":"32","author":"Nattestad","year":"2016","journal-title":"Bioinformatics"},{"key":"2021040616375822500_B35","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: a flexible suite of utilities for comparing genomic features","volume":"26","author":"Quinlan","year":"2010","journal-title":"Bioinformatics"},{"key":"2021040616375822500_B36","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J. Mol. Biol."},{"key":"2021040616375822500_B37","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1101\/gr.170431.113","article-title":"Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans","volume":"24","author":"Roerink","year":"2014","journal-title":"Genome Res."},{"key":"2021040616375822500_B38","doi-asserted-by":"crossref","first-page":"8983","DOI":"10.1073\/pnas.93.17.8983","article-title":"Telomeric repeats (TTAGGC)n are sufficient for chromosome capping function in Caenorhabditis elegans","volume":"93","author":"Wicky","year":"1996","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021040616375822500_B39","first-page":"79","volume-title":"Ann. Genet.","author":"Turleau","year":"1972"},{"key":"2021040616375822500_B40","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1007\/BF00284851","article-title":"New observations on the human and chimpanzee karyotypes","volume":"20","author":"Turleau","year":"1973","journal-title":"Humangenetik"},{"key":"2021040616375822500_B41","doi-asserted-by":"crossref","first-page":"9051","DOI":"10.1073\/pnas.88.20.9051","article-title":"Origin of human chromosome 2: an ancestral telomere-telomere fusion","volume":"88","author":"Ijdo","year":"1991","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"2021040616375822500_B42","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1093\/oxfordjournals.jhered.a109478","article-title":"Robertsonian variation in Mus musculus from central Europe, Spain, and Scotland","volume":"72","author":"Adolph","year":"1981","journal-title":"J. Hered."},{"key":"2021040616375822500_B43","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1038\/35003116","article-title":"Rapid chromosomal evolution in island mice","volume":"403","author":"Britton-Davidian","year":"2000","journal-title":"Nature"},{"key":"2021040616375822500_B44","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1111\/j.1095-8312.2005.00454.x","article-title":"Chromosomal variation in the house mouse","volume":"84","author":"PI\u00e1LEK","year":"2005","journal-title":"Biol. J. Linn. Soc."},{"key":"2021040616375822500_B45","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1111\/jeb.12568","article-title":"On the origin of Robertsonian fusions in nature: evidence of telomere shortening in wild house mice","volume":"28","author":"S\u00e1nchez-Guill\u00e9n","year":"2015","journal-title":"J. Evol. Biol."},{"key":"2021040616375822500_B46","doi-asserted-by":"crossref","first-page":"1499","DOI":"10.1101\/gad.318485.118","article-title":"Adaptation to DNA damage checkpoint in senescent telomerase-negative cells promotes genome instability","volume":"32","author":"Coutelier","year":"2018","journal-title":"Genes Dev."},{"key":"2021040616375822500_B47","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1126\/science.282.5396.2012","article-title":"Genome sequence of the nematode C. elegans: a platform for investigating biology","volume":"282","author":"Consortium*, C.e.S.","year":"1998","journal-title":"Science"},{"key":"2021040616375822500_B48","first-page":"1","article-title":"C. elegans noncoding RNA genes","volume":"25","author":"Stricklin","year":"2005","journal-title":"WormBook"},{"key":"2021040616375822500_B49","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1038\/s41586-020-2547-7","article-title":"Telomere-to-telomere assembly of a complete human X chromosome","volume":"585","author":"Miga","year":"2020","journal-title":"Nature"},{"key":"2021040616375822500_B50","doi-asserted-by":"crossref","first-page":"1309","DOI":"10.1038\/s41587-020-0582-4","article-title":"Automated assembly of centromeres from ultra-long error-prone reads","volume":"38","author":"Bzikadze","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"2021040616375822500_B51","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1038\/nbt.4060","article-title":"Nanopore sequencing and assembly of a human genome with ultra-long reads","volume":"36","author":"Jain","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"2021040616375822500_B52","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1038\/s41587-019-0217-9","article-title":"Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome","volume":"37","author":"Wenger","year":"2019","journal-title":"Nat. Biotechnol."},{"key":"2021040616375822500_B53","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/BF00292267","article-title":"The kinetochores of Caenorhabditis elegans","volume":"86","author":"Albertson","year":"1982","journal-title":"Chromosoma"},{"key":"2021040616375822500_B54","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1101\/gad.571510","article-title":"Dicentric breakage at telomere fusions","volume":"24","author":"Pobiega","year":"2010","journal-title":"Genes Dev."}],"container-title":["Nucleic Acids Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/6\/3338\/36884733\/gkab141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/nar\/article-pdf\/49\/6\/3338\/36884733\/gkab141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T15:25:04Z","timestamp":1617722704000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nar\/article\/49\/6\/3338\/6163097"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,8]]},"references-count":54,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,3,8]]},"published-print":{"date-parts":[[2021,4,6]]}},"URL":"https:\/\/doi.org\/10.1093\/nar\/gkab141","relation":{},"ISSN":["0305-1048","1362-4962"],"issn-type":[{"value":"0305-1048","type":"print"},{"value":"1362-4962","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,4,6]]},"published":{"date-parts":[[2021,3,8]]}}}