Details
- Autor(en) / Beteiligte
- Titel
- Hematopoietic Stem Cell Quiescence Promotes Error-Prone DNA Repair and Mutagenesis
- Ist Teil von
- Cell stem cell, 2010-08, Vol.7 (2), p.174-185
- Ort / Verlag
- Cambridge, MA: Elsevier Inc
- Erscheinungsjahr
- 2010
- Link zum Volltext
- Quelle
- EZB Electronic Journals Library
- Beschreibungen/Notizen
- Most adult stem cells, including hematopoietic stem cells (HSCs), are maintained in a quiescent or resting state in vivo. Quiescence is widely considered to be an essential protective mechanism for stem cells that minimizes endogenous stress caused by cellular respiration and DNA replication. We demonstrate that HSC quiescence can also have detrimental effects. We found that HSCs have unique cell-intrinsic mechanisms ensuring their survival in response to ionizing irradiation (IR), which include enhanced prosurvival gene expression and strong activation of p53-mediated DNA damage response. We show that quiescent and proliferating HSCs are equally radioprotected but use different types of DNA repair mechanisms. We describe how nonhomologous end joining (NHEJ)-mediated DNA repair in quiescent HSCs is associated with acquisition of genomic rearrangements, which can persist in vivo and contribute to hematopoietic abnormalities. Our results demonstrate that quiescence is a double-edged sword that renders HSCs intrinsically vulnerable to mutagenesis following DNA damage. [Display omitted] ► Long-lived HSCs have unique survival mechanisms ► Short-lived myeloid progenitors are poised to die ► Quiescent and proliferating HSCs use different mechanisms of DNA repair ► Quiescent HSCs are intrinsically vulnerable to mutagenesis
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1934-5909eISSN: 1875-9777DOI: 10.1016/j.stem.2010.06.014Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_2924905
- Format
- –
- Schlagworte
- Animals, Biological and medical sciences, Cell Death - radiation effects, Cell differentiation, maturation, development, hematopoiesis, Cell physiology, Cell Proliferation - radiation effects, Cell Survival - radiation effects, DNA Damage, DNA Repair - radiation effects, Fundamental and applied biological sciences. Psychology, Hematopoietic Stem Cells - cytology, Hematopoietic Stem Cells - metabolism, Hematopoietic Stem Cells - radiation effects, Mice, Mice, Inbred C57BL, Molecular and cellular biology, Molecular genetics, Mutagenesis - genetics, Mutagenesis - radiation effects, Mutagenesis. Repair, Myeloid Progenitor Cells - cytology, Myeloid Progenitor Cells - metabolism, Myeloid Progenitor Cells - radiation effects, Radiation Tolerance - radiation effects, Radiation, Ionizing, Recombination, Genetic - radiation effects, Signal Transduction - radiation effects, STEMCELL, Tumor Suppressor Protein p53 - metabolism