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Author Notes:

Corresponding author: shuyi.li2@emory.edu (S. Li); wdynan@emory.edu (W. S. Dynan)

We thank Ms. Yi Hong from Emory University Robert P. Apkarian Integrated Electron Microscopy Core for processing testes samples and collection of electron microcopy images.

Conflict of Interest. The authors declare that there are no conflicts of interest.

Subjects:

Research Funding:

This work was supported by a USPHS R01 grant, CA98239,a US Department of Energy grant, DE-SC0002343, to WSD, and by the Emory University School of Medicine.

The JEOL JEM-1400 electron microscope was acquired with USPHS S10 grant (RR025679 01).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Genetics & Heredity
  • Toxicology
  • NONO
  • Double-strand break repair
  • NHEJ
  • Ionizing radiation
  • Knockout mouse
  • Testes
  • SPLICING-FACTOR
  • DAMAGE RESPONSE
  • GENE-REGULATION
  • PSF
  • REPAIR
  • SPERMATOGENESIS
  • TRANSCRIPTION
  • CONNEXIN-43
  • P54(NRB)
  • COMPLEX

Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes

Tools:

Journal Title:

DNA Repair

Volume:

Volume 51

Publisher:

, Pages 70-78

Type of Work:

Article | Post-print: After Peer Review

Abstract:

The tandem RNA recognition motif protein, NONO, was previously identified as a candidate DNA double-strand break (DSB) repair factor in a biochemical screen for proteins with end-joining stimulatory activity. Subsequent work showed that NONO and its binding partner, SFPQ, have many of the properties expected for bona fide repair factors in cell-based assays. Their contribution to the DNA damage response in intact tissue in vivo has not, however, been demonstrated. Here we compare DNA damage sensitivity in the testes of wild-type mice versus mice bearing a null allele of the NONO homologue (Nono gt ). In wild-type mice, NONO protein was present in Sertoli, peritubular myoid, and interstitial cells, with an increase in expression following induction of DNA damage. As expected for the product of an X-linked gene, NONO was not detected in germ cells. The Nono gt/0 mice had at most a mild testis developmental phenotype in the absence of genotoxic stress. However, following irradiation at sublethal, 2–4 Gy doses, Nono gt/0 mice displayed a number of indicators of radiosensitivity as compared to their wild-type counterparts. These included higher levels of persistent DSB repair foci, increased numbers of apoptotic cells in the seminiferous tubules, and partial degeneration of the blood-testis barrier. There was also an almost complete loss of germ cells at later times following irradiation, evidently arising as an indirect effect reflecting loss of stromal support. Results demonstrate a role for NONO protein in protection against direct and indirect biological effects of ionizing radiation in the whole animal.

Copyright information:

© 2017 Elsevier B.V.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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