Department of Plant Systems Biology, Flanders Institute for Biotechnology (VIB), Gent, Belgium.
PLoS Genet. 2010 Jan 15;6(1):e1000817. doi: 10.1371/journal.pgen.1000817.
The DNA replication process represents a source of DNA stress that causes potentially spontaneous genome damage. This effect might be strengthened by mutations in crucial replication factors, requiring the activation of DNA damage checkpoints to enable DNA repair before anaphase onset. Here, we demonstrate that depletion of the evolutionarily conserved minichromosome maintenance helicase-binding protein ETG1 of Arabidopsis thaliana resulted in a stringent late G2 cell cycle arrest. This arrest correlated with a partial loss of sister chromatid cohesion. The lack-of-cohesion phenotype was intensified in plants without functional CTF18, a replication fork factor needed for cohesion establishment. The synergistic effect of the etg1 and ctf18 mutants on sister chromatid cohesion strengthened the impact on plant growth of the replication stress caused by ETG1 deficiency because of inefficient DNA repair. We conclude that the ETG1 replication factor is required for efficient cohesion and that cohesion establishment is essential for proper development of plants suffering from endogenous DNA stress. Cohesion defects observed upon knockdown of its human counterpart suggest an equally important developmental role for the orthologous mammalian ETG1 protein.
DNA 复制过程代表了 DNA 应激的一个来源，它会导致潜在的自发基因组损伤。这种效应可能会因关键复制因子的突变而增强，需要激活 DNA 损伤检查点，以便在后期 G2 细胞周期开始前进行 DNA 修复。在这里，我们证明了拟南芥中进化保守的微小染色体维持解旋酶结合蛋白 ETG1 的消耗导致严格的晚期 G2 细胞周期阻滞。这种阻滞与姐妹染色单体着丝粒区的部分缺失有关。在没有功能性 CTF18 的植物中，这种缺乏着丝粒的表型更为严重，CTF18 是建立着丝粒所必需的复制叉因子。etg1 和 ctf18 突变体的协同作用对姐妹染色单体着丝粒的影响加强了 ETG1 缺乏引起的复制应激对植物生长的影响，因为 DNA 修复效率低下。我们得出结论，ETG1 复制因子对于有效的着丝粒是必需的，而着丝粒的建立对于遭受内源性 DNA 应激的植物的正常发育是至关重要的。其同源人类 ETG1 蛋白的敲低观察到的着丝粒缺陷表明，它在哺乳动物中也具有同样重要的发育作用。
