Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes
| Autor: | Shourong Zhao, Lahcen Jaafar, William S. Dynan, Shuyi Li, Zhentian Li, Feng-jue Shu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male DNA Repair DNA damage RNA-binding protein Biology Biochemistry Radiation Tolerance Article 03 medical and health sciences chemistry.chemical_compound Mice Radiation Ionizing Testis Animals DNA Breaks Double-Stranded DAPI Radiosensitivity Molecular Biology Gene Mice Knockout RNA recognition motif RNA-Binding Proteins Cell Biology DNA Molecular biology Up-Regulation DNA-Binding Proteins 030104 developmental biology chemistry Gene Expression Regulation Knockout mouse |
| Zdroj: | DNA repair. 51 |
| ISSN: | 1568-7856 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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