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Article

Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population

1
Department for Cancer Research and Molecular Medicine (IKOM), Norwegian University of Science and Technology, 7491 Trondheim, Norway
2
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, 7491 Trondheim, Norway
3
KG Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, 0316 Oslo, Norway
4
Institute of Clinical Medicine, University of Oslo, 0318 Oslo, Norway
*
Author to whom correspondence should be addressed.
Biomolecules 2021, 11(1), 20; https://doi.org/10.3390/biom11010020
Received: 29 November 2020 / Revised: 19 December 2020 / Accepted: 23 December 2020 / Published: 28 December 2020
(This article belongs to the Special Issue DNA Repair and Immune Response)
Non-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damage throughout the cell cycle and is specifically important for homeostasis of post-mitotic neurons and developing lymphocytes. Neuronal apoptosis increases in the mice lacking NHEJ factors Ku70 and Ku80. Inactivation of other NHEJ genes, either Xrcc4 or Lig4, leads to massive neuronal apoptosis in the central nervous system (CNS) that correlates with embryonic lethality in mice. Inactivation of either Paxx, Mri or Dna-pkcs NHEJ gene results in normal CNS development due to compensatory effects of Xlf. Combined inactivation of Xlf/Paxx, Xlf/Mri and Xlf/Dna-pkcs, however, results in late embryonic lethality and high levels of apoptosis in CNS. To determine the impact of NHEJ factors on the early stages of neurodevelopment, we isolated neural stem and progenitor cells from mouse embryos and investigated proliferation, self-renewal and differentiation capacity of these cells lacking either Xlf, Paxx, Dna-pkcs, Xlf/Paxx or Xlf/Dna-pkcs. We found that XRCC4-like factor (XLF), DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and paralogue of XRCC4 and XLF (PAXX) maintain the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models. View Full-Text
Keywords: DNA repair; NHEJ; synthetic lethality; genetic interaction DNA repair; NHEJ; synthetic lethality; genetic interaction
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MDPI and ACS Style

Gago-Fuentes, R.; Oksenych, V. Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population. Biomolecules 2021, 11, 20. https://doi.org/10.3390/biom11010020

AMA Style

Gago-Fuentes R, Oksenych V. Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population. Biomolecules. 2021; 11(1):20. https://doi.org/10.3390/biom11010020

Chicago/Turabian Style

Gago-Fuentes, Raquel, and Valentyn Oksenych. 2021. "Non-Homologous End Joining Factors XLF, PAXX and DNA-PKcs Maintain the Neural Stem and Progenitor Cell Population" Biomolecules 11, no. 1: 20. https://doi.org/10.3390/biom11010020

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