Tasnim Sadia, Kelleher Erin S
Department of Biochemistry and Molecular Biology, Institute for Translational Sciences, The University of Texas Medical Branch, Galveston, TX 77555, United States; Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, United States.
Department of Biology and Biochemistry, University of Houston, Houston, TX 77204, United States.
Dev Biol. 2018 Feb 15;434(2):215-220. doi: 10.1016/j.ydbio.2017.12.021. Epub 2017 Dec 30.
Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain transposable elements in the Drosophila germline. Particularly extreme is the hybrid dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic female ovaries often contain few or no germline cells. Those offspring that are produced from dysgenic germlines exhibit high rates of de novo mutation and recombination, implicating transposition-associated DNA damage as the cause of germline loss. However, how this loss occurs, in terms of the particular cellular response that is triggered (cell cycle arrest, senescence, or cell death) remains poorly understood. We demonstrate that two components of the DNA damage response, Checkpoint kinase 2 and its downstream target p53, determine the frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. We further show that p53 is strongly induced in the germline stem cells (GSCs) of dysgenic females, and is required for their maintenance. Our observations support the critical role for p53 in conferring tolerance of transposable element activity in stem cells.
杂种不育是一种不育综合征，由果蝇生殖系中某些转座元件的激活引起。特别极端的是由P元件DNA转座子引起的杂种不育综合征，其中不育雌性卵巢通常含有很少或没有生殖细胞。那些由不育生殖系产生的后代表现出高频率的新生突变和重组，这表明转座相关的DNA损伤是生殖细胞丢失的原因。然而，就触发的特定细胞反应（细胞周期停滞、衰老或细胞死亡）而言，这种丢失是如何发生的仍知之甚少。我们证明，DNA损伤反应的两个成分，检查点激酶2及其下游靶点p53，决定了与P元件杂种不育相关的卵巢萎缩频率。我们进一步表明，p53在不育雌性的生殖干细胞（GSCs）中被强烈诱导，并且是维持这些细胞所必需的。我们的观察结果支持了p53在赋予干细胞中转座元件活性耐受性方面的关键作用。
