Fission yeast Rnf4 homologs are required for DNA repair
Fission yeast Rnf4 homologs are required for DNA repair
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DOI：
10.1074/jbc.m702652200
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发表时间：
2007-07-13
影响因子：
4.8
通讯作者：
O'Connell, Matthew J.
中科院分区：
文献类型：
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作者：
Kosoy, Ana;Calonge, Teresa M.;O'Connell, Matthew J.
我们描述了裂殖酵母粟酒裂殖酵母中的两种RING指蛋白，Rfp 1和Rfp 2。我们发现这些蛋白质在DNA修复中发挥着冗余的功能。Rfp 1是在双杂交筛选中作为Chk 1相互作用蛋白分离的，并且与Rfp 2具有高度的氨基酸序列相似性。任何一个基因的缺失都不会引起表型，但双缺失（rfp 1 Delta rfp 2 Delta）显示出较差的生存力和细胞周期进展缺陷。这些细胞也对DNA损伤剂敏感，尽管它们保持正常的Chk 1检查点信号。Rfp 1和Rfp 2与人Rnf 4最密切相关，并且我们表明Rnf 4可以在功能上取代Rfp 1和/或Rfp 2。双突变体也显示蛋白SUMO化水平显著增加，我们鉴定了一个S。pombe Ulp 2/Smt 4同源物，当过表达时，降低SUMO水平并抑制rfp 1 Delta rfp 2 Delta细胞的DNA损伤敏感性。
We describe two RING finger proteins in the fission yeast Schizosaccharomyces pombe, Rfp1 and Rfp2. Weshow 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 ( rfp1 Delta rfp2 Delta) 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 rfp1 Delta rfp2 Delta cells.