Institut für Genetik, Universität Hohenheim, Stuttgart, Germany.
Institute of Molecular Biology/CMBI, University of Innsbruck, Innsbruck, Austria.
Sci Rep. 2017 Dec 20;7(1):17890. doi: 10.1038/s41598-017-17973-z.
One of the key players in genome surveillance is the tumour suppressor p53 mediating the adaptive response to a multitude of stress signals. Here we identify Cyclin G (CycG) as co-factor of p53-mediated genome stability. CycG has been shown before to be involved in double-strand break repair during meiosis. Moreover, it is also important for mediating DNA damage response in somatic tissue. Here we find it in protein complexes together with p53, and show that the two proteins interact physically in vitro and in vivo in response to ionizing irradiation. In contrast to mammals, Drosophila Cyclin G is no transcriptional target of p53. Genetic interaction data reveal that p53 activity during DNA damage response requires the presence of CycG. Morphological defects caused by overexpression of p53 are ameliorated in cycG null mutants. Moreover, using a p53 biosensor we show that p53 activity is impeded in cycG mutants. As both p53 and CycG are likewise required for DNA damage repair and longevity we propose that CycG plays a positive role in mediating p53 function in genome surveillance of Drosophila.
在基因组监测中，关键角色之一是肿瘤抑制因子 p53，它介导了对多种应激信号的适应性反应。在这里，我们将细胞周期蛋白 G（CycG）鉴定为 p53 介导的基因组稳定性的辅助因子。以前已经表明，CycG 参与减数分裂期间的双链断裂修复。此外，它对于在体组织中介导 DNA 损伤反应也很重要。在这里，我们发现它与 p53 一起存在于蛋白质复合物中，并表明这两种蛋白质在体外和体内都能响应电离辐射而发生物理相互作用。与哺乳动物不同，果蝇细胞周期蛋白 G 不是 p53 的转录靶标。遗传相互作用数据表明，DNA 损伤反应期间的 p53 活性需要 CycG 的存在。p53 过表达引起的形态缺陷在 cycG 缺失突变体中得到改善。此外，我们使用 p53 生物传感器表明，p53 活性在 cycG 突变体中受到阻碍。由于 p53 和 CycG 同样需要进行 DNA 损伤修复和延长寿命，我们提出 CycG 在介导果蝇基因组监测中的 p53 功能方面发挥积极作用。
