Preprint Article Version 2 Preserved in Portico This version is not peer-reviewed

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

Version 1 : Received: 29 November 2020 / Approved: 1 December 2020 / Online: 1 December 2020 (08:37:50 CET)
Version 2 : Received: 14 December 2020 / Approved: 15 December 2020 / Online: 15 December 2020 (10:41:58 CET)

A peer-reviewed article of this Preprint also exists.

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. 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.

Journal reference: Biomolecules 2020, 11, 20
DOI: 10.3390/biom11010020

Abstract

Non-homologous end-joining (NHEJ) is a major DNA repair pathway in mammalian cells that recognizes, processes and fixes DNA damages 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 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 XLF, DNA-PKcs and PAXX maintain the neural stem and progenitor cell populations and neurodevelopment in mammals, which is particularly evident in the double knockout models.

Subject Areas

DNA repair; NHEJ; synthetic lethality; genetic interaction

Comments (1)

Comment 1
Received: 15 December 2020
Commenter: Valentyn Oksenych
Commenter's Conflict of Interests: Author
Comment: Updated title, discussion, statistical analyses, and Supplementary materials
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