特发性肺纤维化患者的端粒功能障碍与 POT1 有关。

IF 3.6 3区地球科学 Q1 OCEANOGRAPHY Progress in Oceanography Pub Date : 2022-05-02 Epub Date: 2022-04-14 DOI:10.1084/jem.20211681

Joseph Kelich, Tomas Aramburu, Joanne J van der Vis, Louise Showe, Andrew Kossenkov, Jasper van der Smagt, Maarten Massink, Angela Schoemaker, Eric Hennekam, Marcel Veltkamp, Coline H M van Moorsel, Emmanuel Skordalakes

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引用次数: 0

摘要

外显子测序发现了一个特发性肺纤维化（IPF）家族，该家族成员的POT1 p.(L259S)杂合突变以前从未报道过。该家族表现出端粒短和遗传预期。我们发现，POT1(L259S)在端粒悬空结合、核积累、端粒酶负调控和滞后链维持方面存在缺陷。含有该突变的患者细胞表现出端粒缺失、滞后链缺陷、端粒诱导的DNA损伤以及G1停滞的早衰。我们的数据表明，POT1(L259S)是IPF的致病驱动因素，并为基因治疗方案提供了启示。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Telomere dysfunction implicates POT1 in patients with idiopathic pulmonary fibrosis.

Exonic sequencing identified a family with idiopathic pulmonary fibrosis (IPF) containing a previously unreported heterozygous mutation in POT1 p.(L259S). The family displays short telomeres and genetic anticipation. We found that POT1(L259S) is defective in binding the telomeric overhang, nuclear accumulation, negative regulation of telomerase, and lagging strand maintenance. Patient cells containing the mutation display telomere loss, lagging strand defects, telomere-induced DNA damage, and premature senescence with G1 arrest. Our data suggest POT1(L259S) is a pathogenic driver of IPF and provide insights into gene therapy options.

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来源期刊

Progress in Oceanography 地学-海洋学

CiteScore

7.20

自引率

4.90%

发文量

138

审稿时长

3 months

期刊介绍： Progress in Oceanography publishes the longer, more comprehensive papers that most oceanographers feel are necessary, on occasion, to do justice to their work. Contributions are generally either a review of an aspect of oceanography or a treatise on an expanding oceanographic subject. The articles cover the entire spectrum of disciplines within the science of oceanography. Occasionally volumes are devoted to collections of papers and conference proceedings of exceptional interest. Essential reading for all oceanographers.