Tsutsui Y, Khasanov F K, Shinagawa H, Iwasaki H, Bashkirov V I
Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871, Japan.
Genetics. 2001 Sep;159(1):91-105. doi: 10.1093/genetics/159.1.91.
Schizosaccharomyces pombe Rhp55 and Rhp57 are RecA-like proteins involved in double-strand break (DSB) repair. Here we demonstrate that Rhp55 and Rhp57 proteins strongly interact in vivo, similar to Saccharomyces cerevisiae Rad55p and Rad57p. Mutations in the conserved ATP-binding/hydrolysis folds of both the Rhp55 and Rhp57 proteins impaired their function in DNA repair but not in cell proliferation. However, when combined, ATPase fold mutations in Rhp55p and Rhp57p resulted in severe defects of both functions, characteristic of the deletion mutants. Yeast two-hybrid analysis also revealed other multiple in vivo interactions among S. pombe proteins involved in recombinational DNA repair. Similar to S. cerevisiae Rad51p-Rad54p, S. pombe Rhp51p and Rhp54p were found to interact. Both putative Rad52 homologs in S. pombe, Rad22p and Rti1p, were found to interact with the C-terminal region of Rhp51 protein. Moreover, Rad22p and Rti1p exhibited mutual, as well as self-, interactions. In contrast to the S. cerevisiae interacting pair Rad51p-Rad55p, S. pombe Rhp51 protein strongly interacted with Rhp57 but not with Rhp55 protein. In addition, the Rti1 and Rad22 proteins were found to form a complex with the large subunit of S. pombe RPA. Our data provide compelling evidence that most, but not all, of the protein-protein interactions found in S. cerevisiae DSB repair are evolutionarily conserved.
粟酒裂殖酵母的Rhp55和Rhp57是参与双链断裂(DSB)修复的类RecA蛋白。在此我们证明,Rhp55和Rhp57蛋白在体内强烈相互作用,类似于酿酒酵母的Rad55p和Rad57p。Rhp55和Rhp57蛋白保守的ATP结合/水解结构域中的突变损害了它们在DNA修复中的功能,但不影响细胞增殖。然而,当两者结合时,Rhp55p和Rhp57p中的ATP酶结构域突变导致两种功能都出现严重缺陷,这是缺失突变体的特征。酵母双杂交分析还揭示了粟酒裂殖酵母中参与重组DNA修复的其他多种体内相互作用。与酿酒酵母的Rad51p-Rad54p类似,发现粟酒裂殖酵母的Rhp51p和Rhp54p相互作用。在粟酒裂殖酵母中发现的两个假定的Rad52同源物Rad22p和Rti1p,都与Rhp51蛋白的C末端区域相互作用。此外,Rad22p和Rti1p表现出相互作用以及自身相互作用。与酿酒酵母的相互作用对Rad51p-Rad55p不同,粟酒裂殖酵母的Rhp51蛋白与Rhp57强烈相互作用,但与Rhp55蛋白不相互作用。此外,发现Rti1和Rad22蛋白与粟酒裂殖酵母RPA的大亚基形成复合物。我们的数据提供了令人信服的证据,表明酿酒酵母DSB修复中发现的大多数(但不是全部)蛋白质-蛋白质相互作用在进化上是保守的。