Shwachman-Diamond Syndrome Protein SBDS Maintains Human Telomeres by Regulating Telomerase Recruitment

Publication date: 13 February 2018
Source:Cell Reports, Volume 22, Issue 7
Author(s): Yi Liu, Feng Liu, Yizhao Cao, Huimin Xu, Yangxiu Wu, Su Wu, Dan Liu, Yong Zhao, Zhou Songyang, Wenbin Ma
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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Teaser

The mutation of Shwachman-Bodian-Diamond syndrome (SBDS) gene is a major causative reason for Shwachman-Diamond syndrome (SDS). Liu et al. show that SBDS is a cell cycle-dependent telomere-protecting protein that facilitates TPP1-mediated telomerase recruitment, revealing the underlying mechanism of telomere shortening found in SDS patients.


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