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首页> 外文期刊>Cell cycle >Genetic and physical interactions between the yeast ELG1 gene and orthologs of the Fanconi anemia pathway
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Genetic and physical interactions between the yeast ELG1 gene and orthologs of the Fanconi anemia pathway

机译：酵母ELG1基因与Fanconi贫血途径的直系同源基因之间的遗传和物理相互作用

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摘要

Fanconi anemia (FA) is a human syndrome characterized by genomic instability and increased incidence of cancer. FA is a genetically heterogeneous disease caused by mutations in at least 15 different genes; several of these genes are conserved in the yeast Saccharomyces cerevisiae. Elg1 is also a conserved protein that forms an RFC-like complex, which interacts with SUMOylated PCNA. The mammalian Elg1 protein has been recently found to interact with the FA complex. Here we analyze the genetic interactions between elg1AΔ and mutants of the yeast FA-like pathway. We show that Elg1 physically contacts the Mhf1/Mhf2 histone-like complex and genetically interacts with MPH1 (ortholog of the FANCM helicase) and CHL1 (ortholog of the FANCJ helicase) genes. We analyze the sensitivity of double, triple, quadruple and quintuple mutants to methylmethane sulfonate (MMS) and to hydroxyurea (HU). Our results show that genetic interactions depend on the type of DNA damaging agent used and show a hierarchy: Chl1 and Elg1 play major roles in the survival to these genotoxins and exhibit synthetic fitness reduction. Mph1 plays a lesser role, and the effect of the Mhf1/2 complex is seen only in the absence of Elg1 on HU-containing medium. Finally, we dissect the relationship between yeast FA-like mutants and the replication clamp, PCNA. Our results point to an intricate network of interactions rather than a single, linear repair pathway.
机译：范可尼贫血（FA）是一种人类综合征，其特征是基因组不稳定和癌症发病率增加。 FA是一种遗传异质性疾病，由至少15个不同基因的突变引起;这些基因中的几个在酿酒酵母中是保守的。 Elg1也是一种保守的蛋白质，可形成类似于RFC的复合物，并与SUMOylated PCNA相互作用。最近发现哺乳动物的Elg1蛋白与FA复合物相互作用。在这里，我们分析了elg1AΔ和酵母FA样途径的突变体之间的遗传相互作用。我们显示Elg1物理接触Mhf1 / Mhf2组蛋白样复合物，并与MPH1（FANCM解旋酶的直系同源物）和CHL1（FANCJ解旋酶的直系同源物）基因发生遗传相互作用。我们分析了对甲基甲烷磺酸盐（MMS）和对羟基脲（HU）的双重，三重，四重和五重突变体的敏感性。我们的结果表明，遗传相互作用取决于所使用的DNA破坏剂的类型，并显示出等级关系：Chl1和Elg1在这些基因毒素的存活中起主要作用，并表现出合成适应性降低。 Mph1的作用较小，只有在含HU的培养基上没有Elg1时才能看到Mhf1 / 2复合物的作用。最后，我们剖析了酵母FA样突变体与复制钳PCNA之间的关系。我们的研究结果指出了复杂的相互作用网络，而不是单一的线性修复途径。

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