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Cell Rep. 2018 Feb 13;22(7):1849-1860. doi: 10.1016/j.celrep.2018.01.057.

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

Author information

1
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.
2
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: liufeng23@mail.sysu.edu.cn.
3
Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
4
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China; Collaborative Innovation Center for Cancer Medicine, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510006, China; Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: songyang@bcm.edu.
5
Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Oncology in South China, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China; Collaborative Innovation Center for Cancer Medicine, Institute of Healthy Aging Research, Sun Yat-sen University, Guangzhou 510006, China. Electronic address: mawenbin@mail.sysu.edu.cn.

Abstract

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.

KEYWORDS:

SBDS; SDS; TPP1; telomerase; telomere

PMID:
29444436
PMCID:
PMC5844287
DOI:
10.1016/j.celrep.2018.01.057
[Indexed for MEDLINE]
Free PMC Article

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