College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
College of Life Science and Technology, Huazhong Agricultural University, Wuhan 430070, China
Proc Natl Acad Sci U S A. 2018 Apr 17;115(16):E3837-E3845. doi: 10.1073/pnas.1720094115. Epub 2018 Apr 2.
DNA damage poses a serious threat to genome integrity and greatly affects growth and development. To maintain genome stability, all organisms have evolved elaborate DNA damage response mechanisms including activation of cell cycle checkpoints and DNA repair. Here, we show that the DNA repair protein SNI1, a subunit of the evolutionally conserved SMC5/6 complex, directly links these two processes in SNI1 binds to the activation domains of E2F transcription factors, the key regulators of cell cycle progression, and represses their transcriptional activities. In turn, E2Fs activate the expression of , suggesting that E2Fs and SNI1 form a negative feedback loop. Genetically, overexpression of SNI1 suppresses the phenotypes of E2F-overexpressing plants, and loss of E2F function fully suppresses the mutant, indicating that SNI1 is necessary and sufficient to inhibit E2Fs. Altogether, our study revealed that SNI1 is a negative regulator of E2Fs and plays dual roles in DNA damage responses by linking cell cycle checkpoint and DNA repair.
DNA 损伤对基因组完整性构成严重威胁，并极大地影响生长和发育。为了维持基因组稳定性，所有生物体都进化出了精细的 DNA 损伤反应机制，包括细胞周期检查点的激活和 DNA 修复。在这里，我们表明 DNA 修复蛋白 SNI1 是进化上保守的 SMC5/6 复合物的一个亚基，它直接将这两个过程联系在一起。SNI1 结合到 E2F 转录因子的激活结构域，E2F 转录因子是细胞周期进程的关键调节剂，并抑制它们的转录活性。反过来，E2Fs 激活的表达，表明 E2Fs 和 SNI1 形成一个负反馈环。遗传上，过量表达 SNI1 抑制了 E2F 过表达植物的表型，而 E2F 功能的丧失则完全抑制了突变体，表明 SNI1 是抑制 E2Fs 所必需和充分的。总的来说，我们的研究表明 SNI1 是 E2Fs 的负调节剂，并通过连接细胞周期检查点和 DNA 修复在 DNA 损伤反应中发挥双重作用。
