Abstract
AbstractGenetic damage in the germline induced by P-element mobilization causes a syndrome known as P-M hybrid dysgenesis (HD), which manifests as elevated mutation frequency and loss of germline cells. In this study, we found that Myc plays an important role in eliminating germline cells in the context of HD. P-element mobilization resulted in downregulation of Myc expression in the germline. Myc knockdown caused germline elimination; conversely, Myc overexpression rescued the germline loss caused by P-element mobilization. Moreover, restoration of fertility by Myc resulted in the production of gametes with elevated mutation frequency and reduced ability to undergo development. Our results demonstrate that Myc downregulation mediates elimination of germline cells with accumulated genetic damage, and that failure to remove these cells results in increased production of aberrant gametes. Therefore, we propose that elimination of germline cells mediated by Myc downregulation is a quality control mechanism that maintains the genomic integrity of the germline.
Funder
MEXT | Japan Society for the Promotion of Science
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
Reference56 articles.
1. Gartner, A., Milstein, S., Ahmed, S., Hodgkin, J. & Hengartner, M. O. A conserved checkpoint pathway mediates DNA damage-induced apoptosis and cell cycle arrest in C. elegans. Mol. Cell 5, 435–443 (2000).
2. Sutovsky, P. et al. A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis. J. Cell Sci. 114, 1665–1675 (2001).
3. Titus, S. et al. Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans. Sci. Transl. Med. 5, 172ra21 (2013).
4. Chu, H. P. et al. Germline quality control: eEF2K stands guard to eliminate defective oocytes. Dev. Cell 28, 561–572 (2014).
5. Pal-Bhadra, M. et al. Heterochromatic silencing and HP1 localization in Drosophila are dependent on the RNAi machinery. Science 303, 669–672 (2004).
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