Year: 2016
Type: article
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.
DOI: 10.1172/jci84547
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: Leukemia and Lymphoma Society, University of Michigan, National Institutes of Health, College of Pharmacy, University of Michigan, National Institute on Aging, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Allergy and Infectious Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Division of Cancer Epidemiology and Genetics, National Cancer Institute
Awards: G141600148, G1516671061, G2351744653, G2551785263, G4376152923, G4584014668, G491642029, G5391971805, Molecular functions of the shelterin component ACD/TPP1 in somatic stem cells and tissue homeostasis, G791431752, G9000002557, G9000006758, G9000031400, G9000087397, G9000308391, G9000347736
OpenAlex ID: W2345010388