Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba, Ibaraki, 305-8577, Japan.
Graduate School of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8572, Japan.
Commun Biol. 2020 Apr 22;3(1):185. doi: 10.1038/s42003-020-0923-3.
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.
由 P 元件转座引起的生殖系遗传损伤导致一种称为 P-M 杂种不育(HD)的综合征,其表现为突变频率升高和生殖细胞丢失。在这项研究中,我们发现 Myc 在 HD 背景下在消除生殖细胞中起重要作用。P 元件转座导致生殖系中 Myc 表达下调。Myc 敲低导致生殖系消除;相反,Myc 过表达挽救了 P 元件转座引起的生殖系丢失。此外,Myc 的恢复生育能力导致突变频率升高和发育能力降低的配子产生。我们的结果表明,Myc 下调介导积累遗传损伤的生殖细胞的消除,并且未能去除这些细胞导致异常配子的产生增加。因此,我们提出由 Myc 下调介导的生殖细胞消除是维持生殖系基因组完整性的质量控制机制。