Abstract
Genetic 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.
Highlights
Genetic 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
There is no known link between DNA damage response and Bruno, a regulator of oogenesis[23,24,25], Bruno activity is required for the germline stem cells (GSCs) loss phenotype in adult HD females[26]
Reduction of Myc expression in the germline caused the germline-loss phenotype; overexpression of Myc restored fertility impaired by HD, resulting in production of gametes with elevated mutation frequency and reduced ability to develop into offspring
Summary
Genetic 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. Reduction of Myc expression in the germline caused the germline-loss phenotype; overexpression of Myc restored fertility impaired by HD, resulting in production of gametes with elevated mutation frequency and reduced ability to develop into offspring. These observations strongly suggest that elimination of germline cells mediated by Myc downregulation plays an important role in maintaining the genomic integrity of the germline
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