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

Here, 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 themore » 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.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [1]
  1. Emory Univ. School of Medicine, Atlanta, GA (United States)
  2. Columbus Pathology, Columbus, GA (United States)
Publication Date:
Grant/Contract Number:
SC0002343
Type:
Accepted Manuscript
Journal Name:
DNA Repair
Additional Journal Information:
Journal Volume: 51; Journal Issue: C; Journal ID: ISSN 1568-7864
Publisher:
Elsevier
Research Org:
Georgia Health Sciences Univ. Research Inst., Inc., Augusta, GA (United States)
Sponsoring Org:
USDOE; USPHS
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; NONO; Double-strand break repair; NHEJ; Ionizing radiation; Knockout mouse; Testes
OSTI Identifier:
1465173
Alternate Identifier(s):
OSTI ID: 1415506

Li, Shuyi, Shu, Feng-jue, Li, Zhentian, Jaafar, Lahcen, Zhao, Shourong, and Dynan, William S. Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes. United States: N. p., Web. doi:10.1016/j.dnarep.2017.02.002.
Li, Shuyi, Shu, Feng-jue, Li, Zhentian, Jaafar, Lahcen, Zhao, Shourong, & Dynan, William S. Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes. United States. doi:10.1016/j.dnarep.2017.02.002.
Li, Shuyi, Shu, Feng-jue, Li, Zhentian, Jaafar, Lahcen, Zhao, Shourong, and Dynan, William S. 2017. "Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes". United States. doi:10.1016/j.dnarep.2017.02.002. https://www.osti.gov/servlets/purl/1465173.
@article{osti_1465173,
title = {Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes},
author = {Li, Shuyi and Shu, Feng-jue and Li, Zhentian and Jaafar, Lahcen and Zhao, Shourong and Dynan, William S.},
abstractNote = {Here, 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 (Nonogt). 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 Nonogt/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, Nonogt/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.},
doi = {10.1016/j.dnarep.2017.02.002},
journal = {DNA Repair},
number = C,
volume = 51,
place = {United States},
year = {2017},
month = {2}
}