The shelterin complex and hematopoiesis

J Clin Invest. 2016 May 2;126(5):1621-9. doi: 10.1172/JCI84547. Epub 2016 May 2.


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.

Publication types

  • Review

MeSH terms

  • Anemia, Aplastic* / genetics
  • Anemia, Aplastic* / metabolism
  • Animals
  • Bone Marrow Diseases* / genetics
  • Bone Marrow Diseases* / metabolism
  • Bone Marrow Failure Disorders
  • Chromosomes, Human
  • DNA Damage
  • Dyskeratosis Congenita* / genetics
  • Dyskeratosis Congenita* / metabolism
  • Hematopoiesis / genetics*
  • Hemoglobinuria, Paroxysmal* / genetics
  • Hemoglobinuria, Paroxysmal* / metabolism
  • Humans
  • Mutation*
  • Telomere* / genetics
  • Telomere* / metabolism
  • Telomere-Binding Proteins* / genetics
  • Telomere-Binding Proteins* / metabolism


  • ACD protein, human
  • TINF2 protein, human
  • Telomere-Binding Proteins
  • shelterin, human

Supplementary concepts

  • Bone Marrow failure syndromes