Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating Telomerase Recruitment.
Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating Telomerase Recruitment.
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Shwachman-Diamond 综合征蛋白 SBDS 通过调节端粒酶募集来维持人类端粒
DOI：
10.1016/j.celrep.2018.01.057
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发表时间：
2018-02-13
期刊：
影响因子：
8.8
通讯作者：
Ma W
中科院分区：
文献类型：
--
作者：
Liu Y;Liu F;Cao Y;Xu H;Wu Y;Wu S;Liu D;Zhao Y;Songyang Z;Ma W
Shwachman-Diamond综合征是一种罕见的儿科疾病，以包括造血功能障碍在内的各种全身性疾病为特征。Shwachman-Bodian-Diamond综合征(SBDS)基因突变被认为是导致抑郁症的主要原因。尽管有报道称SBDS患者的粒细胞端粒长度较短，但其潜在机制仍不清楚。在这里，我们提供数据来阐明SBDS在端粒保护中的作用。我们证明了SBDS缺乏会导致端粒缩短。我们发现，疾病相关的SBDS突变体的过表达或SBDS的敲除阻碍了端粒酶在端粒上的募集，而端粒酶的整体逆转录酶活性没有受到影响。此外，我们还发现在细胞周期的S期，SBDS可以特异性地与TPP1结合，可能是TPP1与端粒酶相互作用的稳定剂。我们的发现表明，SBDS是一种端粒保护蛋白，参与调节端粒酶的招募。
Shwachman-Diamond syndrome (SDS) is a rare pediatric disease characterized by various systemic disorders, including hematopoietic dysfunction. The mutation of Shwachman-Bodian-Diamond syndrome (SBDS) gene has been proposed to be a major causative reason for SDS. Although SBDS patients were reported to have shorter telomere length in granulocytes, the underlying mechanism is still unclear. Here we provide data to elucidate the role of SBDS in telomere protection. We demonstrate that SBDS deficiency leads to telomere shortening. We found that overexpression of disease-associated SBDS mutants or knockdown of SBDS hampered the recruitment of telomerase onto telomeres, while the overall reverse transcriptase activity of telomerase remained unaffected. Moreover, we show that SBDS could specifically bind to TPP1 during the S phase of cell cycle, likely functioning as a stabilizer for TPP1-telomerase interaction. Our findings suggest that SBDS is a telomere-protecting protein that participates in regulating telomerase recruitment.
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影响因子：
7
作者：
Lee, Ok-Hee;Kim, Hyeung;Zhou Songyang
通讯作者：
Zhou Songyang
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Lingner, Joachim
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Savage SA
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作者：
FENG, JL;FUNK, WD;VILLEPONTEAU, B
通讯作者：
VILLEPONTEAU, B