A SUMO-like domain protein, Esc2, is required for genome integrity and sister chromatid cohesion in Saccharomyces cerevisiae
A SUMO-like domain protein, Esc2, is required for genome integrity and sister chromatid cohesion in Saccharomyces cerevisiae
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DOI：
10.1534/genetics.107.086249
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发表时间：
2008-09-01
期刊：
影响因子：
3.3
通讯作者：
Hishida, Takashi
中科院分区：
文献类型：
--
作者：
Ohya, Tomoko;Arai, Hirokazu;Hishida, Takashi
ESC 2基因编码具有两个串联C末端SUMO样结构域的蛋白质，并且从酵母到人类都是保守的。先前的研究表明Esc 2参与基因沉默。在这里，我们探讨了SUMO样结构域的功能意义，并描述了Esc 2在DNA复制过程中促进基因组完整性的新作用。这项研究表明，esc 2 δ细胞对羟基脲（HU）适度敏感，姐妹染色单体凝聚力有缺陷，寿命缩短，这些效应通过删除RRM 3基因（Pif 1样DNA解旋酶）得到增强。esc 2 Delta rrm 3 Delta细胞也有严重的生长缺陷，并在S/G晚期积累DNA损伤（2）。相反，esc 2 Delta不增强mrc 1 Delta细胞中的HU敏感性或姐妹染色单体凝聚缺陷，而是部分抑制这两种表型。我们还表明，Esc 2 SUMO样结构域的缺失使Esc 2蛋白不稳定，并在功能上使Esc 2失活，但这种表型被具有真实SUMO结构域的Esc 2变体抑制。这些结果表明，Esc 2是功能等同于一个稳定的SUMO融合蛋白，并在促进DNA复制叉的进展和姐妹染色单体凝聚力，否则会阻碍复制叉在rrm 3 δ细胞中发挥重要作用。
The ESC2 gene encodes a protein with two tandem C-terminal SUMO-like domains and is conserved from yeasts to humans. Previous Studies have implicated Esc2 in gene silencing. Here, we explore the functional significance of SUMO-like domains and describe a novel role for Esc2 in promoting genome integrity during DNA replication. This study shows that esc2 Delta cells are modestly sensitive to hydroxy urea (HU) and defective in sister chromatid cohesion and have a reduced life span, and these effects are enhanced by deletion of the RRM3 gene that is a Pif1-like DNA helicase. esc2 Delta rrm3 Delta cells also have a severe growth defect and accumulate DNA damage in late S/G(2). In contrast, esc2 Delta does not enhance the HU sensitivity or sister chromatid cohesion defect in mrc1 Delta cells, but rather partially suppresses both phenotypes. We also show that deletion of both Esc2 SUMO-like domains destabilizes Esc2 protein and functionally inactivates Esc2, but this phenotype is suppressed by an Esc2 variant with an authentic SUMO domain. These results suggest that Esc2 is functionally equivalent to a stable SUMO fusion protein and plays important roles in facilitating DNA replication fork progression and sister chromatid cohesion that would otherwise impede the replication fork in rrm3 Delta cells.