Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Division of Cell Biology and Biophysics, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, MO, USA; School of BioSciences, University of Melbourne, Parkville, VIC, Australia.
Gene. 2019 Oct 30;717:144043. doi: 10.1016/j.gene.2019.144043. Epub 2019 Aug 7.
Genes involved in the repair of DNA damage are emerging as playing important roles during the disease processes caused by pathogenic fungi. However, there are potentially hundreds of genes involved in DNA repair in a fungus and some of those genes can play additional roles within the cell. One such gene is RAD23, required for virulence of the human pathogenic fungus Cryptococcus neoformans, that encodes a protein involved in the nucleotide excision repair (NER) pathway. However, Rad23 is a dual function protein, with a role in either repair of damaged DNA or protein turn over by directing proteins to the proteasome. Here, these two functions of Rad23 were tested by the creation of a series of domain deletion alleles of RAD23 and the assessment of the strains for DNA repair, proteasome functions, and virulence properties. Deletion of the different domains was able to uncouple the two functions of Rad23, and the phenotypes of strains carrying such forms indicated that the role of RAD23 in virulence is due to its function in proteasomal-mediated protein degradation rather than NER.
参与 DNA 损伤修复的基因在致病性真菌引起的疾病过程中起着重要作用。然而，真菌中可能有数百个参与 DNA 修复的基因，其中一些基因在细胞内可能发挥额外的作用。RAD23 就是这样一个基因，它是人类致病性真菌新生隐球菌毒力所必需的，它编码一种参与核苷酸切除修复 (NER) 途径的蛋白质。然而，Rad23 是一种具有双重功能的蛋白质，它可以通过将蛋白质导向蛋白酶体来修复受损的 DNA 或参与蛋白质周转。在这里，通过创建一系列 RAD23 的结构域缺失等位基因，并评估这些菌株的 DNA 修复、蛋白酶体功能和毒力特性，对 Rad23 的这两种功能进行了测试。不同结构域的缺失能够使 Rad23 的两种功能分离，携带这些形式的菌株的表型表明，RAD23 在毒力中的作用是由于其在蛋白酶体介导的蛋白质降解中的功能，而不是 NER。
