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

Abstract

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 the blood-testis barrier. Theremore » 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:

Li, Shuyi ^[1]; Shu, Feng-jue ^[1]; Li, Zhentian ^[1]; Jaafar, Lahcen ^[1]; Zhao, Shourong ^[2]; Dynan, William S. ^[1]

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+ Show Author Affiliations

1. Emory Univ. School of Medicine, Atlanta, GA (United States)
2. Columbus Pathology, Columbus, GA (United States)

Publication Date:

Fri Feb 10 00:00:00 EST 2017

Research Org.:

Georgia Health Sciences Univ. Research Inst., Inc., Augusta, GA (United States)

Sponsoring Org.:

USDOE; USPHS

OSTI Identifier:

1465173

Alternate Identifier(s):

OSTI ID: 1415506

Grant/Contract Number:  

SC0002343

Resource Type:

Accepted Manuscript

Journal Name:

DNA Repair

Additional Journal Information:

Journal Volume: 51; Journal Issue: C; Journal ID: ISSN 1568-7864

Publisher:

Elsevier

Country of Publication:

United States

Language:

English

Subject:

59 BASIC BIOLOGICAL SCIENCES; NONO; Double-strand break repair; NHEJ; Ionizing radiation; Knockout mouse; Testes