دورية أكاديمية
TINF2 is a haploinsufficient tumor suppressor that limits telomere length
| العنوان: | TINF2 is a haploinsufficient tumor suppressor that limits telomere length |
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| المؤلفون: | Isabelle Schmutz, Arjen R Mensenkamp, Kaori K Takai, Maaike Haadsma, Liesbeth Spruijt, Richarda M de Voer, Seunga Sara Choo, Franziska K Lorbeer, Emma J van Grinsven, Dirk Hockemeyer, Marjolijn CJ Jongmans, Titia de Lange |
| المصدر: | eLife, Vol 9 (2020) |
| بيانات النشر: | eLife Sciences Publications Ltd, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine LCC:Science LCC:Biology (General) |
| مصطلحات موضوعية: | cancer predisposition, TIN2, telomere length, Medicine, Science, Biology (General), QH301-705.5 |
| الوصف: | Telomere shortening is a presumed tumor suppressor pathway that imposes a proliferative barrier (the Hayflick limit) during tumorigenesis. This model predicts that excessively long somatic telomeres predispose to cancer. Here, we describe cancer-prone families with two unique TINF2 mutations that truncate TIN2, a shelterin subunit that controls telomere length. Patient lymphocyte telomeres were unusually long. We show that the truncated TIN2 proteins do not localize to telomeres, suggesting that the mutations create loss-of-function alleles. Heterozygous knock-in of the mutations or deletion of one copy of TINF2 resulted in excessive telomere elongation in clonal lines, indicating that TINF2 is haploinsufficient for telomere length control. In contrast, telomere protection and genome stability were maintained in all heterozygous clones. The data establish that the TINF2 truncations predispose to a tumor syndrome. We conclude that TINF2 acts as a haploinsufficient tumor suppressor that limits telomere length to ensure a timely Hayflick limit. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2050-084X |
| العلاقة: | https://elifesciences.org/articles/61235Test; https://doaj.org/toc/2050-084XTest |
| DOI: | 10.7554/eLife.61235 |
| الوصول الحر: | https://doaj.org/article/fefee7f4f78a4dcf9950c74585342521Test |
| رقم الانضمام: | edsdoj.fefee7f4f78a4dcf9950c74585342521 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 2050084X |
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| DOI: | 10.7554/eLife.61235 |