Luo Lingfei, Uerlings Yvonne, Happel Nicole, Asli Naisana S, Knoetgen Hendrik, Kessel Michael
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Mol Cell Biol. 2007 Jul;27(13):4737-44. doi: 10.1128/MCB.00123-07. Epub 2007 Apr 30.
The geminin protein functions both as a DNA rereplication inhibitor through association with Cdt1 and as a repressor of Hox gene transcription through the polycomb pathway. Here, we report that the functions of avian geminin are coordinated with and regulated by cell cycle-dependent nuclear-cytoplasmic shuttling. In S phase, geminin enters nuclei and inhibits both loading of the minichromosome maintenance (MCM) complex onto chromatin and Hox gene transcription. At the end of mitosis, geminin is exported from nuclei by the exportin protein Crm1 and is unavailable in the nucleus during the next G(1) phase, thus ensuring proper chromatin loading of the MCM complex and Hox gene transcription. This mechanism for regulating the functions of geminin adds to distinct mechanisms, such as protein degradation and ubiquitination, applied in other vertebrates.
双微体蛋白通过与Cdt1结合发挥DNA再复制抑制剂的作用，并通过多梳途径作为Hox基因转录的阻遏物。在此，我们报道禽类双微体蛋白的功能与细胞周期依赖性核质穿梭协调并受其调控。在S期，双微体蛋白进入细胞核，抑制微小染色体维持（MCM）复合物加载到染色质上以及Hox基因转录。在有丝分裂末期，双微体蛋白被输出蛋白Crm1从细胞核中输出，并且在下一个G1期在细胞核中不可用，从而确保MCM复合物正确加载到染色质上以及Hox基因转录。这种调节双微体蛋白功能的机制增加了在其他脊椎动物中应用的不同机制，如蛋白质降解和泛素化。
