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The shelterin complex and hematopoiesis
Morgan Jones, … , Catherine E. Keegan, Ivan Maillard
Morgan Jones, … , Catherine E. Keegan, Ivan Maillard
Published May 2, 2016
Citation Information: J Clin Invest. 2016;126(5):1621-1629. https://doi.org/10.1172/JCI84547.
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The shelterin complex and hematopoiesis

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Abstract

Mammalian chromosomes terminate in stretches of repetitive telomeric DNA that act as buffers to avoid loss of essential genetic information during end-replication. A multiprotein complex known as shelterin prevents recognition of telomeric sequences as sites of DNA damage. Telomere erosion contributes to human diseases ranging from BM failure to premature aging syndromes and cancer. The role of shelterin telomere protection is less understood. Mutations in genes encoding the shelterin proteins TRF1-interacting nuclear factor 2 (TIN2) and adrenocortical dysplasia homolog (ACD) were identified in dyskeratosis congenita, a syndrome characterized by somatic stem cell dysfunction in multiple organs leading to BM failure and other pleiotropic manifestations. Here, we introduce the biochemical features and in vivo effects of individual shelterin proteins, discuss shelterin functions in hematopoiesis, and review emerging knowledge implicating the shelterin complex in hematological disorders.

Authors

Morgan Jones, Kamlesh Bisht, Sharon A. Savage, Jayakrishnan Nandakumar, Catherine E. Keegan, Ivan Maillard

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Figure 3

Schematic representation of human proteins affected by germline mutations in dyskeratosis congenita and related disorders.

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Schematic representation of human proteins affected by germline mutation...
Mutations affecting 11 different proteins have been reported to date in dyskeratosis congenita and related disorders, as indicated by colored structures. TERT, TERC, dyskerin, NHP2, NOP10, and TCAB1 are important for the processing, integrity, and/or function of the telomerase holoenzyme, a ribonucleoprotein complex containing TERC RNA and the catalytic TERT protein with reverse transcriptase activity. TIN2 and TPP1 (encoded by ACD) are members of the shelterin complex (see Figure 1). CTC1 belongs to a complex that regulates telomere C-strand synthesis and telomere replication. RTEL1 is important for telomere replication and stability. PARN was recently described to control processing of TERC RNA as well as mRNAs of other telomere maintenance genes.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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