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International Journal of Hematology
Published in: International Journal of Hematology 6/2018

01-06-2018 | Progress in Hematology

The role of telomere binding molecules for normal and abnormal hematopoiesis

Authors: Kentaro Hosokawa, Fumio Arai

Published in: International Journal of Hematology | Issue 6/2018

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Abstract

In order to maintain the homeostasis of the hematopoietic system, hematopoietic stem cells (HSCs) need to be maintained while slowly dividing over their lifetime. However, repeated cell divisions lead to the gradual accumulation of DNA damage and ultimately impair HSC function. Since telomeres are particularly fragile when subjected to replication stress, cells have several defense machinery to protect telomeres. Moreover, HSCs must protect their genome against possible DNA damage, while maintaining telomere length. A group of proteins called the shelterin complex are deeply involved in this two-way role, and it is highly resistant to the replication stress to which HSCs are subjected. Most shelterin-deficient experimental models suffer acute cytotoxicity and severe phenotypes, as each shelterin component is essential for telomere protection. The Tin2 point mutant mice show a dyskeratosis congenita (DC) like phenotype, and the Tpp1 deletion impairs the hematopoietic system. POT1/Pot1a is highly expressed in HSCs and contributes to the maintenance of the HSC pool during in vitro culture. Here, we discuss the role of shelterin molecules in HSC regulation and review current understanding of how these are regulated in the maintenance of the HSC pool and the development of hematological disorders.
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Metadata
Title
The role of telomere binding molecules for normal and abnormal hematopoiesis
Authors
Kentaro Hosokawa
Fumio Arai
Publication date
01-06-2018
Publisher
Springer Japan
Published in
International Journal of Hematology / Issue 6/2018
Print ISSN: 0925-5710
Electronic ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-018-2432-4

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