{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:40:54Z","timestamp":1785210054234,"version":"3.55.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T00:00:00Z","timestamp":1592179200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1729\/13"],"award-info":[{"award-number":["1729\/13"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["2071\/18"],"award-info":[{"award-number":["2071\/18"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100001698","name":"Israel Cancer Research Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001698","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011713","name":"Worldwide Cancer Research","doi-asserted-by":"publisher","award":["15-0338"],"award-info":[{"award-number":["15-0338"]}],"id":[{"id":"10.13039\/100011713","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006245","name":"Ministry of Science and Technology, Israel","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006245","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001645","name":"Boehringer Ingelheim Fonds","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001645","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Inserm","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004099","name":"Ligue Nationale contre le Cancer","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004099","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Telomeres cap the ends of eukaryotic chromosomes and distinguish them from broken DNA ends to suppress DNA damage response, cell cycle arrest and genomic instability. Telomeres are elongated by telomerase to compensate for incomplete replication and nuclease degradation and to extend the proliferation potential of germ and stem cells and most cancers. However, telomeres in somatic cells gradually shorten with age, ultimately leading to cellular senescence. Hoyeraal-Hreidarsson syndrome (HHS) is characterized by accelerated telomere shortening and diverse symptoms including bone marrow failure, immunodeficiency, and neurodevelopmental defects. HHS is caused by germline mutations in telomerase subunits, factors essential for its biogenesis and recruitment to telomeres, and in the helicase RTEL1. While diverse phenotypes were associated with RTEL1 deficiency, the telomeric role of RTEL1 affected in HHS is yet unknown. Inducible ectopic expression of wild-type RTEL1 in patient fibroblasts rescued the cells, enabled telomerase-dependent telomere elongation and suppressed the abnormal cellular phenotypes, while silencing its expression resulted in gradual telomere shortening. Our observations reveal an essential role of the RTEL1 C-terminus in facilitating telomerase action at the telomeric 3\u2032 overhang. Thus, the common etiology for HHS is the compromised telomerase action, resulting in telomere shortening and reduced lifespan of telomerase positive cells.<\/jats:p>","DOI":"10.1093\/nar\/gkaa503","type":"journal-article","created":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T19:15:39Z","timestamp":1591125339000},"source":"Crossref","is-referenced-by-count":15,"title":["Full length RTEL1 is required for the elongation of the single-stranded telomeric overhang by telomerase"],"prefix":"10.1093","author":[{"given":"Aya","family":"Awad","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Galina","family":"Glousker","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Lamm","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shadi","family":"Tawil","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noa","family":"Hourvitz","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riham","family":"Smoom","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0758-8022","authenticated-orcid":false,"given":"Patrick","family":"Revy","sequence":"first","affiliation":[{"name":"INSERM UMR 1163, Laboratory of Genome Dynamics in the Immune System, Equipe Labellis\u00e9e Ligue contre le Cancer and Paris Descartes-Sorbonne Paris Cit\u00e9 University, Imagine Institute, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7720-435X","authenticated-orcid":false,"given":"Yehuda","family":"Tzfati","sequence":"first","affiliation":[{"name":"Department of Genetics, The Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Givat Ram, Jerusalem\u00a091904, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,6,15]]},"reference":[{"key":"2020061514333045800_B1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1146\/annurev-genet-032918-021921","article-title":"Shelterin-mediated telomere protection","volume":"52","author":"de\u00a0Lange","year":"2018","journal-title":"Annu. 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