Department of Microbiology & Immunology, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10065, USA.
DNA Repair (Amst). 2013 Jul;12(7):472-9. doi: 10.1016/j.dnarep.2013.04.027. Epub 2013 May 28.
Recent studies implicate a number of DNA repair proteins in mammalian telomere maintenance. However, because several key repair proteins in mammals are missing from the well-studied budding and fission yeast, their roles at telomeres cannot be modeled in standard fungi. In this report, we explored the dimorphic fungus Ustilago maydis as an alternative model for telomere research. This fungus, which belongs to the phylum Basidiomycota, has a telomere repeat unit that is identical to the mammalian repeat, as well as a constellation of DNA repair proteins that more closely mimic the mammalian collection. We showed that the two core components of homology-directed repair (HDR) in U. maydis, namely Brh2 and Rad51, both promote telomere maintenance in telomerase positive cells, just like in mammals. In addition, we found that Brh2 is localized to telomeres in vivo, suggesting that it acts directly at chromosome ends. We surveyed a series of mutants with DNA repair defects, and found many of them to have short telomeres. Our results indicate that factors involved in DNA repair are probably also needed for optimal telomere maintenance in U. maydis, and that this fungus is a useful alternative model system for telomere research.
最近的研究表明,许多 DNA 修复蛋白参与了哺乳动物端粒的维持。然而,由于在研究充分的芽殖酵母和裂殖酵母中缺少几种关键的修复蛋白,因此无法在标准真菌中模拟它们在端粒上的作用。在本报告中,我们探索了二型真菌构巢曲霉作为端粒研究的替代模型。这种真菌属于担子菌门,其端粒重复单元与哺乳动物的重复单元完全相同,并且具有一系列更类似于哺乳动物集合的 DNA 修复蛋白。我们表明,构巢曲霉中同源定向修复(HDR)的两个核心组成部分,即 Brh2 和 Rad51,都像在哺乳动物中一样促进端粒酶阳性细胞中的端粒维持。此外,我们发现 Brh2 在体内定位于端粒,表明它直接作用于染色体末端。我们调查了一系列具有 DNA 修复缺陷的突变体,发现其中许多突变体的端粒较短。我们的结果表明,参与 DNA 修复的因子可能也是构巢曲霉中端粒最佳维持所必需的,并且该真菌是端粒研究的有用替代模型系统。