Stead Kristen, Aguilar Cristina, Hartman Theresa, Drexel Melissa, Meluh Pamela, Guacci Vincent
Basic Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
J Cell Biol. 2003 Nov 24;163(4):729-41. doi: 10.1083/jcb.200305080. Epub 2003 Nov 17.
Pds5p and the cohesin complex are required for sister chromatid cohesion and localize to the same chromosomal loci over the same cell cycle window. However, Pds5p and the cohesin complex likely have distinct roles in cohesion. We report that pds5 mutants establish cohesion, but during mitosis exhibit precocious sister dissociation. Thus, unlike the cohesin complex, which is required for cohesion establishment and maintenance, Pds5p is required only for maintenance. We identified SMT4, which encodes a SUMO isopeptidase, as a high copy suppressor of both the temperature sensitivity and precocious sister dissociation of pds5 mutants. In contrast, SMT4 does not suppress temperature sensitivity of cohesin complex mutants. Pds5p is SUMO conjugated, with sumoylation peaking during mitosis. SMT4 overexpression reduces Pds5p sumoylation, whereas smt4 mutants have increased Pds5p sumoylation. smt4 mutants were previously shown to be defective in cohesion maintenance during mitosis. These data provide the first link between a protein required for cohesion, Pds5p, and sumoylation, and suggest that Pds5p sumoylation promotes the dissolution of cohesion.
Pds5p和黏连蛋白复合体对于姐妹染色单体黏连是必需的，并且在同一个细胞周期窗口内定位于相同的染色体位点。然而，Pds5p和黏连蛋白复合体在黏连中可能具有不同的作用。我们报道，pds5突变体能够建立黏连，但在有丝分裂期间表现出过早的姐妹染色单体解离。因此，与建立和维持黏连所必需的黏连蛋白复合体不同，Pds5p仅在维持黏连时是必需的。我们鉴定出编码一种SUMO异肽酶的SMT4，它是pds5突变体温度敏感性和过早姐妹染色单体解离的高拷贝抑制子。相比之下，SMT4不能抑制黏连蛋白复合体突变体的温度敏感性。Pds5p是SUMO化修饰的，其SUMO化修饰在有丝分裂期间达到峰值。SMT4的过表达降低了Pds5p的SUMO化修饰，而smt4突变体中Pds5p的SUMO化修饰增加。之前已表明smt4突变体在有丝分裂期间的黏连维持方面存在缺陷。这些数据首次揭示了黏连所需蛋白Pds5p与SUMO化修饰之间的联系，并表明Pds5p的SUMO化修饰促进了黏连的解除。
