Unknown

Dataset Information

0

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


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.

SUBMITTER: Li S 

PROVIDER: S-EPMC5379473 | BioStudies | 2017-01-01T00:00:00Z

SECONDARY ACCESSION(S): 614238

REPOSITORIES: biostudies

Similar Datasets

2014-01-01 | S-EPMC4150768 | BioStudies
1000-01-01 | S-EPMC5371645 | BioStudies
2004-01-01 | S-EPMC517883 | BioStudies
2016-01-01 | S-EPMC4990234 | BioStudies
2015-01-01 | S-EPMC4349251 | BioStudies
2020-01-01 | S-EPMC7226794 | BioStudies
2013-01-01 | S-EPMC3579931 | BioStudies
2012-01-01 | S-EPMC3488241 | BioStudies
1000-01-01 | S-EPMC3711201 | BioStudies
2016-01-01 | S-EPMC5415080 | BioStudies