| First Author | Li S | Year | 2017 |
| Journal | DNA Repair (Amst) | Volume | 51 |
| Pages | 70-78 | PubMed ID | 28209515 |
| Mgi Jnum | J:253307 | Mgi Id | MGI:6109725 |
| Doi | 10.1016/j.dnarep.2017.02.002 | Citation | Li S, et al. (2017) Cell-type specific role of the RNA-binding protein, NONO, in the DNA double-strand break response in the mouse testes. DNA Repair (Amst) 51:70-78 |
| abstractText | 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. |
