Skibbens R V, Corson L B, Koshland D, Hieter P
Department of Molecular Biology and Genetics, The Johns Hopkins School of Medicine, Baltimore, Maryland 21205 USA.
Genes Dev. 1999 Feb 1;13(3):307-19. doi: 10.1101/gad.13.3.307.
CTF7 (chromosome transmission fidelity) gene in budding yeast encodes an essential protein that is required for high-fidelity chromosome transmission and contains regions of identity conserved from yeast to man. ctf7 mutant cells arrested prior to anaphase onset contain separated sister chromatids. Thus, Ctf7p is essential for cohesion. Cohesion is established during S phase and then maintained until mitosis. However, Ctf7p activity is required only during S phase, suggesting that Ctf7p functions in the establishment of cohesion. In addition, ctf7 genetically interacts with DNA metabolism mutations pol30 (PCNA) and ctf18 (an RF-C like protein) and ctf7 temperature sensitivity and chromosome loss are rescued by high levels of POL30. These findings provide the first evidence that links the establishment of sister chromatid cohesion to the DNA replication machinery and suggest that the assembly of cohesion (and possibly condensation) complexes are coupled to PCNA-dependent DNA replication. The analysis of Ctf7p also reveals an important connection between sister chromatid cohesion, spindle integrity and the spindle assembly checkpoint.
芽殖酵母中的CTF7（染色体传递保真度）基因编码一种对高保真染色体传递至关重要的必需蛋白，并且包含从酵母到人类保守的同源区域。在后期开始前停滞的ctf7突变细胞含有分离的姐妹染色单体。因此，Ctf7p对黏连是必需的。黏连在S期建立，然后维持到有丝分裂。然而，Ctf7p活性仅在S期需要，这表明Ctf7p在黏连的建立中起作用。此外，ctf7与DNA代谢突变pol30（增殖细胞核抗原）和ctf18（一种类RF-C蛋白）发生遗传相互作用，并且高水平的POL30可挽救ctf7的温度敏感性和染色体丢失。这些发现提供了首个将姐妹染色单体黏连的建立与DNA复制机制联系起来的证据，并表明黏连（可能还有凝聚）复合物的组装与依赖增殖细胞核抗原的DNA复制相关联。对Ctf7p的分析还揭示了姐妹染色单体黏连、纺锤体完整性和纺锤体组装检查点之间的重要联系。
