ArticleStem cells (Dayton, Ohio)2014
Exonuclease 1 is a critical mediator of survival during DNA double strand break repair in nonquiescent hematopoietic stem and progenitor cells.
Article in Stem cells (Dayton, Ohio), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Novel candidate metastasis-associated genes for synovial sarcoma.Journal of cellular and molecular medicine · 2024Article
- DNA Damage Responses, the Trump Card of Stem Cells in the Survival Game.Advances in experimental medicine and biology · 2024Review
- The FBXO32/ATR/ATM axis acts as a molecular switch to control the sensitivity of osteosarcoma cells to irradiation through its regulation of EXO1 expression.Acta biochimica et biophysica Sinica · 2023Article
- Tocotrienol Rich Fraction Supplementation Modulate Brain Hippocampal Gene Expression in APPswe/PS1dE9 Alzheimer's Disease Mouse Model.Journal of Alzheimer's disease : JAD · 2019Article
- Hypoxia pathway genetic variants predict survival of non-small-cell lung cancer patients receiving platinum-based chemotherapy.Carcinogenesis · 2017Article
- Cellularly active N-hydroxyurea FEN1 inhibitors block substrate entry to the active site.Nature chemical biology · 2016Article
- Expression analysis of radiation-responsive genes in human hematopoietic stem/progenitor cells.Journal of radiation research · 2016Article
- Functional analysis of the nasopharyngeal carcinoma primary tumor‑associated gene interaction network.Molecular medicine reports · 2015Article
- Replication stress in MLL-rearrangements.Oncoscience · 2015Article
- Leukemogenic rearrangements at the mixed lineage leukemia gene (MLL)-multiple rather than a single mechanism.Frontiers in cell and developmental biology · 2015Review
- Article
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3 authors at 2 institutions in 1 country.
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Abstract
Hematopoietic stem cell (HSC) populations require DNA repair pathways to maintain their long-term survival and reconstitution capabilities, but mediators of these processes are still being elucidated. Exonuclease 1 (Exo1) participates in homologous recombination (HR) and Exo1 loss results in impaired 5' HR end resection. We use cultured Exo1(mut) fibroblasts and bone marrow to demonstrate that loss of Exo1 function results in defective HR in cycling cells. Conversely, in Exo1(mut) mice HR is not required for maintenance of quiescent HSCs at steady state, confirming the steady state HSC reliance on nonhomologous end joining (NHEJ). Exo1(mut) mice sustained serial repopulation, displayed no defect in competitive repopulation or niche occupancy, and exhibited no increased sensitivity to whole body ionizing radiation. However, when Exo1(mut) HSCs were pushed into cell cycle in vivo with 5-fluorouracil or poly IC, the hematopoietic population became hypersensitive to IR, resulting in HSC defects and animal death. We propose Exo1-mediated HR is dispensable for stem cell function in quiescent HSC, whereas it is essential to HSC response to DNA damage processing after cell cycle entry, and its loss is not compensated by intact NHEJ. In HSCs, the maintenance of stem cell function after DNA damage is dependent on the DNA repair capacity, segregated by active versus quiescent points in cell cycle.
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