Dai Junbiao, Xie Weiwu, Brady Troy L, Gao Jiquan, Voytas Daniel F
Department of Genetics, Development, and Cell Biology, 1035A Roy J. Carver Co-Laboratory, Iowa State University, Ames, IA 50011-3650, USA.
Department of Genetics, Development, and Cell Biology, 1035A Roy J. Carver Co-Laboratory, Iowa State University, Ames, IA 50011-3650, USA.
Mol Cell. 2007 Jul 20;27(2):289-299. doi: 10.1016/j.molcel.2007.06.010.
The yeast Ty5 retrotransposon preferentially integrates into heterochromatin at the telomeres and silent mating loci. Target specificity is mediated by a small domain of Ty5 integrase (the targeting domain, TD), which interacts with the heterochromatin protein Sir4 and tethers the integration complex to target sites. Here we demonstrate that TD is phosphorylated and that phosphorylation is required for interaction with Sir4. The yeast cell, therefore, through posttranslational modification, controls Ty5's mutagenic potential: when TD is phosphorylated, insertions occur in gene-poor heterochromatin, thereby minimizing deleterious consequences of transposition; however, in the absence of phosphorylation, Ty5 integrates throughout the genome, frequently causing mutations. TD phosphorylation is reduced under stress conditions, specifically starvation for amino acids, nitrogen, or fermentable carbon. This suggests that Ty5 target specificity changes in response to nutrient availability and is consistent with McClintock's hypothesis that mobile elements restructure host genomes as an adaptive response to environmental challenge.
酵母Ty5逆转录转座子优先整合到端粒和沉默交配位点的异染色质中。靶标特异性由Ty5整合酶的一个小结构域（靶向结构域，TD）介导，该结构域与异染色质蛋白Sir4相互作用，并将整合复合体连接到靶位点。在此我们证明TD被磷酸化，且磷酸化是与Sir4相互作用所必需的。因此，酵母细胞通过翻译后修饰来控制Ty5的诱变潜力：当TD被磷酸化时，插入发生在基因贫乏的异染色质中，从而将转座的有害后果降至最低；然而，在没有磷酸化的情况下，Ty5整合到整个基因组中，经常导致突变。在应激条件下，特别是氨基酸、氮或可发酵碳饥饿时，TD磷酸化会减少。这表明Ty5靶标特异性会根据营养物质的可利用性而改变，这与麦克林托克的假说一致，即移动元件会重组宿主基因组，作为对环境挑战的适应性反应。
