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裂殖酵母Rnf4同源物是DNA修复所必需的。

Fission yeast Rnf4 homologs are required for DNA repair.

作者信息

Kosoy Ana, Calonge Teresa M, Outwin Emily A, O'Connell Matthew J

机构信息

Department of Oncological Sciences, Mount Sinai School of Medicine, One Gustave L. Levy Place, New York, NY 10029, USA.

出版信息

J Biol Chem. 2007 Jul 13;282(28):20388-94. doi: 10.1074/jbc.M702652200. Epub 2007 May 14.

Abstract

We describe two RING finger proteins in the fission yeast Schizosaccharomyces pombe, Rfp1 and Rfp2. We show that these proteins function redundantly in DNA repair. Rfp1 was isolated as a Chk1-interacting protein in a two-hybrid screen and has high amino acid sequence similarity to Rfp2. Deletion of either gene does not cause a phenotype, but a double deletion (rfp1Deltarfp2Delta) showed poor viability and defects in cell cycle progression. These cells are also sensitive to DNA-damaging agents, although they maintained normal checkpoint signaling to Chk1. Rfp1 and Rfp2 are most closely related to human Rnf4, and we showed that Rnf4 can substitute functionally for Rfp1 and/or Rfp2. The double mutants also showed significantly increased levels of protein SUMOylation, and we identified an S. pombe Ulp2/Smt4 homolog that, when overexpressed, reduced SUMO levels and suppressed the DNA damage sensitivity of rfp1Delta rfp2Delta cells.

摘要

我们描述了裂殖酵母粟酒裂殖酵母中的两种泛素连接酶结构域蛋白,Rfp1和Rfp2。我们发现这些蛋白在DNA修复中发挥冗余功能。Rfp1在双杂交筛选中作为一种与Chk1相互作用的蛋白被分离出来,并且与Rfp2具有高度的氨基酸序列相似性。单个基因的缺失不会导致表型变化,但双缺失(rfp1Δrfp2Δ)显示出活力不佳以及细胞周期进程缺陷。这些细胞对DNA损伤剂也敏感,尽管它们维持了对Chk1的正常检查点信号传导。Rfp1和Rfp2与人类Rnf4关系最为密切,并且我们表明Rnf4在功能上可以替代Rfp1和/或Rfp2。双突变体还显示出蛋白质SUMO化水平显著增加,并且我们鉴定出一种粟酒裂殖酵母Ulp2/Smt4同源物,当它过表达时,会降低SUMO水平并抑制rfp1Δrfp2Δ细胞对DNA损伤的敏感性。

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