Simonicova Lucia, Dudekova Henrieta, Ferenc Jaroslav, Prochazkova Katarina, Nebohacova Martina, Dusinsky Roman, Nosek Jozef, Tomaska Lubomir
Department of Genetics, Faculty of Natural Sciences, Comenius University, Mlynska dolina, B-1, 84215, Bratislava, Slovak Republic.
Department of Biochemistry, Faculty of Natural Sciences, Comenius University, Mlynska dolina, CH-1, 84215, Bratislava, Slovak Republic.
Curr Genet. 2015 Nov;61(4):517-27. doi: 10.1007/s00294-014-0472-8. Epub 2015 Jan 8.
The experimental evidence from the last decade made telomerase a prominent member of a family of moonlighting proteins performing different functions at various cellular loci. However, the study of extratelomeric functions of the catalytic subunit of mammalian telomerase (TERT) is often complicated by the fact that it is sometimes difficult to distinguish them from its role(s) at the chromosomal ends. Here, we present an experimental model for studying the extranuclear function(s) of mammalian telomerase in the yeast Saccharomyces cerevisiae. We demonstrate that the catalytic subunit of mammalian telomerase protects the yeast cells against oxidative stress and affects the stability of the mitochondrial genome. The advantage of using S. cerevisiae to study of mammalian telomerase is that (1) mammalian TERT does not interfere with its yeast counterpart in the maintenance of telomeres, (2) yeast telomerase is not localized in mitochondria and (3) it does not seem to be involved in the protection of cells against oxidative stress and stabilization of mtDNA. Thus, yeast cells can be used as a 'test tube' for reconstitution of mammalian TERT extranuclear function(s).
过去十年的实验证据表明，端粒酶是兼职蛋白家族中的重要成员，在不同细胞位点发挥不同功能。然而，对哺乳动物端粒酶催化亚基（TERT）的端粒外功能进行研究时，常因有时难以将其与在染色体末端的作用区分开来而变得复杂。在此，我们提出了一个用于研究哺乳动物端粒酶在酿酒酵母中的核外功能的实验模型。我们证明，哺乳动物端粒酶的催化亚基可保护酵母细胞免受氧化应激，并影响线粒体基因组的稳定性。利用酿酒酵母研究哺乳动物端粒酶的优势在于：（1）哺乳动物TERT在维持端粒时不干扰其酵母对应物；（2）酵母端粒酶不在线粒体中定位；（3）它似乎不参与保护细胞免受氧化应激和稳定线粒体DNA。因此，酵母细胞可作为重组哺乳动物TERT核外功能的“试管”。
