[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-371574-105":3,"detail-sidebar-cat-0-en-105":81,"doc-detail-371574-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":74,"head_meta":76,"extra_data":78,"updated_unix":80},105,"en","reading-the-dna-of-telomeres-insight-cancer","Reading the DNA of telomeres - Insight Cancer","","Experiments using DNA-damage detection tools uncover distinctive but conserved telomere features in cancer cells that maintain chromosome ends through Alternative Lengthening of Telomeres (ALT). By repurposing the END-seq sequencing workflow, researchers identify telomeric reads consistent with one-ended double-strand-break-like signals and show ALT ends closely resemble those in telomerase-reliant and non-cancer cells. The study highlights a conserved 5’ ATC terminus, G-overhang organization, and internal ssDNA enrichment specific to ALT-positive cells.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/healthcare/","Healthcare",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/reading-the-dna-of-telomeres-insight-cancer/371574/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/reading-the-dna-of-telomeres-insight-cancer/371574.png","ImageObject",300,407,{"name":42,"@type":43},"Sarah ","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-22","2026-09-23",true,{"@type":52,"interactionType":53,"userInteractionCount":55},"InteractionCounter",{"@type":54},"ViewAction",7,{"@type":57,"mainEntity":58},"FAQPage",[59,65,69],{"name":60,"@type":61,"acceptedAnswer":62},"Why must cancer cells maintain telomere length to proliferate?","Question",{"text":63,"@type":64},"Cancer cells need functional telomeres to act as protective chromosome-end caps. In most normal somatic cells telomeres shorten with each division, eventually restricting proliferation and limiting tumor development.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How do ALT-positive cancers maintain telomeres without telomerase?",{"text":68,"@type":64},"ALT-positive cancers use a specialized DNA repair pathway that lengthens telomeres by copying DNA from a longer telomere within the same cell, rather than relying on telomerase.",{"name":70,"@type":61,"acceptedAnswer":71},"What is the purpose of repurposing END-seq in this study?",{"text":72,"@type":64},"The work repurposes END-seq to detect telomeres as one-ended reads, enabling identification of telomeric reads defined by unidirectionality and repeated TTAGGG or CCCTAA motifs.","https://schema.org",{"og:url":32,"og:type":75,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":77,"canonical":32},"index,follow",{"doc_id":79,"site_id":7},371574,1791303944,{"code":4,"msg":82,"data":83},"success",[84,88,92,96,101,106,109,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":85,"show_sort_weight":86,"slug":87},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":89,"show_sort_weight":90,"slug":91},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":93,"show_sort_weight":94,"slug":95},"Exam",70,"exam",{"id":97,"doc_module":4,"doc_module_name":25,"category_name":98,"show_sort_weight":99,"slug":100},5,"Comic",60,"comic",{"id":102,"doc_module":4,"doc_module_name":25,"category_name":103,"show_sort_weight":104,"slug":105},6,"Technology",50,"technology",{"id":55,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":107,"slug":108},40,"healthcare",{"id":110,"doc_module":4,"doc_module_name":25,"category_name":111,"show_sort_weight":112,"slug":113},8,"Research & Report",30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":97,"slug":129},19,"General","general",{"code":4,"msg":82,"data":131},{"doc_id":79,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":55,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":55,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":30,"language":139,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":140,"faqs":141,"seo_title":142,"seo_description":12,"update_tm":143,"read_time":110},962085320529,"https://ap-avatar.wpscdn.com/davatar_9964176cb1d06d4a9deccf72a44ae3dc","INSIGHT  \nCANCER  \nReading the DNA of telomeres  \nExperiments with tools designed to detect DNA damage reveal unique and conserved features of telomeres in cancer cells.  \nSHAMAYITA ROY AND CLAUS M AZZALIN  \n Copyright Roy and Azzalin. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.  \nRelated research article Azeroglu B, Wu W, Pavani R, Sandhu R, Matsumoto T, Nussenzweig A, Lazzerini Denchi E.  \n2025. Conserved and unique features of terminal telomeric sequences in ALT-positive cancer cells. eLife 14:RP106657 . doi:  \n10.7554/eLife.106657  \nTo proliferate uncontrollably, cancer cells  \nneed to maintain the length of their telo  \nmeres, regions of DNA that act as protective “caps” at the ends of chromosomes. In most healthy somatic cells, telomeres shorten slightly after every cell division. Once a finite number of divisions has been reached, telomeres become critically short and halt any further proliferation, creating a barrier to cancer development (Harley et al., 1990; Jones-Weinert et al., 2025) .  \nApproximately 85% of human cancers overcome this barrier by activating telomerase, an enzyme that extends telomeres but is not normally expressed in somatic cells. The remaining cancers rely on a specialized DNA repair pathway called Alternative Lengthening of Telomeres (or ALT for short), which elongates short telomeres by copying DNA from a longer telomere within the same cell (Dilley et al., 2016; O’Sullivan and Greenberg, 2025) .  \nTelomeres consist of two strands of DNA, which each contain a specific sequence of base pairs: TTAGGG and its complementary strand CCCTAA. At the end of the telomere, the strand rich in the base guanine (G) extends past its complementary strand to form a single-stranded  \nregion of 50–200 bases, known as the G-overhang (Figure 1; Jones-Weinert et al., 2025) . While the general structure of telomeres is well characterized, much less is understood about how the telomeres of ALT-positive cancer cells differ from those that rely on telomerase (ALTnegative cells) . Now, in eLife, Eros Lazzerini Denchi and colleagues at the National Cancer Institute – including Benura Azeroglu as first author – report repurposing an established DNA sequencing method to investigate key features of telomeres in these different types of cancer cell (Azeroglu et al., 2025) .  \nThe team employed END-seq, a powerful sequencing method which was originally developed to map double-stranded breaks across the genome (Wong et al., 2021) . Since the end of chromosomes resemble one end of a doublestranded break, END-seq should identify telomeres as unidirectional reads rather than the bidirectional reads that characterize typical double-stranded breaks. By using this technique on human cell lines that express telomerase, Azeroglu et al. confirmed it could identify ‘telomeric reads’, which were defined based on whether they were unidirectional and contained at least four consecutive TTAGGG (G-rich) or CCCTAA (C-rich) repeats. Almost all of the identified telomeric reads derived from the C-rich strand, as would be expected when looking at telomeres as one-ended double-stranded breaks, confirming the robustness of the approach.  \nApplying this technique to a variety of cancerous and non-cancerous cell lines as well as mouse tissues revealed that the ends of chromosomes in ALT-positive cells are remarkably similar to those in ALT-negative and non-cancerous cells.  \nRoy and Azzalin. eLife 2025;14:e107648. DOI: [https://doi.org/10.7554/eLife.107648](https://doi.org/10.7554/eLife.107648) 1 of 3  \n Insight Cancer | Reading the DNA of telomeres  \nFigure 1. Unique and conserved telomere features in cancer cells that use different telomere maintenance mechanisms. In cancer cells, the telomeres (red) covering the end of chromosomes (black) are maintained and lengthened by either the ALT pathway (A","cbCaikJ3Ztaar5VO","https://ap.wps.com/l/cbCaikJ3Ztaar5VO","pdf",483800,"English","# Insight Cancer | Reading the DNA of telomeres\n## Telomere maintenance in cancer cells\n## Telomere structure and key features\n## END-seq strategy for telomeric reads\n## Conserved versus ALT-specific telomere characteristics\n## POT1 effects and implications","[{\"question\":\"Why must cancer cells maintain telomere length to proliferate?\",\"answer\":\"Cancer cells need functional telomeres to act as protective chromosome-end caps. In most normal somatic cells telomeres shorten with each division, eventually restricting proliferation and limiting tumor development.\"},{\"question\":\"How do ALT-positive cancers maintain telomeres without telomerase?\",\"answer\":\"ALT-positive cancers use a specialized DNA repair pathway that lengthens telomeres by copying DNA from a longer telomere within the same cell, rather than relying on telomerase.\"},{\"question\":\"What is the purpose of repurposing END-seq in this study?\",\"answer\":\"The work repurposes END-seq to detect telomeres as one-ended reads, enabling identification of telomeric reads defined by unidirectionality and repeated TTAGGG or CCCTAA motifs.\"}]","Reading the DNA of telomeres - Insight Cancer | PDF",1790192356]