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Telomeres enable complete replication of chromosome ends while shielding the termini from DNA repair factors and innate immune surveillance systems that would otherwise recognize them as damaged or foreign DNA. A particular threat is posed by Mre11\u2010Rad50, a nuclease complex conserved from bacteria to humans that specializes in the detection and processing of DNA ends. The solutions to these DNA end\u2010related challenges that have emerged across the tree of life converge on a small number of recurring strategies. Here, we review how diverse biological systems, from bacteriophages to mammals, have solved the DNA end\u2010related challenges, with a particular focus on recent advances in our understanding of end protection.<\/jats:p>","DOI":"10.1002\/bies.70197","type":"journal-article","created":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T14:41:12Z","timestamp":1792593672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Taming Mre11\u2013Rad50 at Telomeres: Convergent Strategies for Chromosome\u2010End Protection Across Evolution"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8390-2485","authenticated-orcid":false,"given":"Florian","family":"Roisn\u00e9\u2010Hamelin","sequence":"first","affiliation":[{"name":"Department of Fundamental Microbiology (DMF) Faculty of Biology and Medicine (FBM) University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0150-0395","authenticated-orcid":false,"given":"Stephan","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Fundamental Microbiology (DMF) Faculty of Biology and Medicine (FBM) University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,21]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041685"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2022.03.008"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20221395"},{"key":"e_1_2_14_5_1","article-title":"Lessons From Yeast: Mechanisms of Telomere Length Regulation","volume":"60","author":"Mayangsari R.","year":"2026","journal-title":"Annual Review of Genetics"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.137851"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0092\u20108674(03)00083\u20107"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genet\u2010061323\u2010044915"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/genetics\/106.2.185"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41422\u2010018\u20100110\u2010y"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100382\u2010x"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.REV119.008583"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574\u20106968.2000.tb09095.x"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2017.11.025"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873\u20103468.13695"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/v12090996"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20220754"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s44318\u2010025\u201000593\u2010z"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022\u20105193(73)90198\u20107"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a010108"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tig.2023.07.008"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.mdna3\u20100023\u20102014"},{"key":"e_1_2_14_23_1","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1016\/0092-8674(87)90576-9","article-title":"The Telomere Terminal Transferase of Tetrahymena Is a ribonucleoprotein Enzyme With Two Kinds of Primer Specificity","volume":"51","author":"Greider C. 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