ArticleProceedings of the National Academy of Sciences of the United States of America2014
Differential role of nonhomologous end joining factors in the generation, DNA damage response, and myeloid differentiation of human induced pluripotent stem cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 37 citations in OpenAlex.
- The multifaceted functions of DNA-PKcs: implications for the therapy of human diseases.MedComm · 2024Review
- To investigate the mechanism of Yiwei Decoction in the treatment of premature ovarian insufficiency-related osteoporosis using transcriptomics, network pharmacology and molecular docking techniques.Scientific reports · 2023Article
- Biomarkers of DNA Damage Response Enable Flow Cytometry-Based Diagnostic to Identify Inborn DNA Repair Defects in Primary Immunodeficiencies.Journal of clinical immunology · 2022Article
- Spatiotemporal 7q11.23 protein network analysis implicates the role of DNA repair pathway during human brain development.Scientific reports · 2021Article
- Article
- Reprogramming and differentiation-dependent transcriptional alteration of DNA damage response and apoptosis genes in human induced pluripotent stem cells.Journal of radiation research · 2019Article
- Hematopoietic Stem Cell Transplantation for DNA Double Strand Breakage Repair Disorders.Frontiers in pediatrics · 2019Review
- The Genomic Health of Human Pluripotent Stem Cells: Genomic Instability and the Consequences on Nuclear Organization.Frontiers in genetics · 2018Review
- Article
- Induced Pluripotent Stem Cells: Advances in the Quest for Genetic Stability during Reprogramming Process.International journal of molecular sciences · 2017Review
- Inhibiting DNA-PKcs in a non-homologous end-joining pathway in response to DNA double-strand breaks.Oncotarget · 2017Article
- Comparison of the early response of human embryonic stem cells and human induced pluripotent stem cells to ionizing radiation.Molecular medicine reports · 2017Article
- Gene Editing Approaches against Viral Infections and Strategy to Prevent Occurrence of Viral Escape.PLoS pathogens · 2016Review
- CRISPaint allows modular base-specific gene tagging using a ligase-4-dependent mechanism.Nature communications · 2016Article
- Rad51 Regulates Reprogramming Efficiency through DNA Repair Pathway.Development & reproduction · 2016Article
- Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals.Journal of clinical immunology · 2016Article
- LIG4 mediates Wnt signalling-induced radioresistance.Nature communications · 2016Article
- Loss of H3K9me3 Correlates with ATM Activation and Histone H2AX Phosphorylation Deficiencies in Hutchinson-Gilford Progeria Syndrome.PloS one · 2016Article
- Radiation-sensitive severe combined immunodeficiency: The arguments for and against conditioning before hematopoietic cell transplantation--what to do?The Journal of allergy and clinical immunology · 2015Article
- Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines.Nucleic acids research · 2015Article
Corrections and comments
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Authors and funding
18 authors at 11 institutions in 6 countries.
Funding
Abstract
Nonhomologous end-joining (NHEJ) is a key pathway for efficient repair of DNA double-strand breaks (DSBs) and V(D)J recombination. NHEJ defects in humans cause immunodeficiency and increased cellular sensitivity to ionizing irradiation (IR) and are variably associated with growth retardation, microcephaly, and neurodevelopmental delay. Repair of DNA DSBs is important for reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). To compare the specific contribution of DNA ligase 4 (LIG4), Artemis, and DNA-protein kinase catalytic subunit (PKcs) in this process and to gain insights into phenotypic variability associated with these disorders, we reprogrammed patient-derived fibroblast cell lines with NHEJ defects. Deficiencies of LIG4 and of DNA-PK catalytic activity, but not Artemis deficiency, were associated with markedly reduced reprogramming efficiency, which could be partially rescued by genetic complementation. Moreover, we identified increased genomic instability in LIG4-deficient iPSCs. Cell cycle synchronization revealed a severe defect of DNA repair and a G0/G1 cell cycle arrest, particularly in LIG4- and DNA-PK catalytically deficient iPSCs. Impaired myeloid differentiation was observed in LIG4-, but not Artemis- or DNA-PK-mutated iPSCs. These results indicate a critical importance of the NHEJ pathway for somatic cell reprogramming, with a major role for LIG4 and DNA-PKcs and a minor, if any, for Artemis.
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Registered trials
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