Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes
- Emory Univ. School of Medicine, Atlanta, GA (United States)
- Columbus Pathology, Columbus, GA (United States)
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.
- Research Organization:
- Georgia Health Sciences Univ. Research Inst., Inc., Augusta, GA (United States)
- Sponsoring Organization:
- USDOE; USPHS
- Grant/Contract Number:
- SC0002343
- OSTI ID:
- 1465173
- Alternate ID(s):
- OSTI ID: 1415506
- Journal Information:
- DNA Repair, Vol. 51, Issue C; ISSN 1568-7864
- Publisher:
- ElsevierCopyright Statement
- Country of Publication:
- United States
- Language:
- English
Web of Science
RNF8 mediates NONO degradation following UV-induced DNA damage to properly terminate ATR-CHK1 checkpoint signaling
|
journal | November 2018 |
Interaction of modified oligonucleotides with nuclear proteins, formation of novel nuclear structures and sequence-independent effects on RNA processing
|
posted_content | March 2019 |
The RXFP3 receptor is functionally associated with cellular responses to oxidative stress and DNA damage
|
journal | December 2019 |
Similar Records
Testicular peritubular cells in culture secrete specific inhibitor(s) of plasminogen activators
Mutations that affect meiosis in male mice influence the dynamics of the mid-preleptotene and bouquet stages