Microbiology, Department of Biomedical Sciences, Faculty of Sciences, University of Extremadura, Badajoz, Spain.
PLoS One. 2011;6(8):e23732. doi: 10.1371/journal.pone.0023732. Epub 2011 Aug 23.
The heterodimeric Ku complex has been shown to participate in DNA repair and telomere regulation in a variety of organisms. Here we report a detailed characterization of the function of Ku70 in the diploid fungal pathogen Candida albicans. Both ku70 heterozygous and homozygous deletion mutants have a wild-type colony and cellular morphology, and are not sensitive to MMS or UV light. Interestingly, we observed complex effects of KU70 gene dosage on telomere lengths, with the KU70/ku70 heterozygotes exhibiting slightly shorter telomeres, and the ku70 null strain exhibiting long and heterogeneous telomeres. Analysis of combination mutants suggests that the telomere elongation in the ku70 null mutant is due mostly to unregulated telomerase action. In addition, elevated levels of extrachromosomal telomeric circles were detected in the null mutant, consistent with activation of aberrant telomeric recombination. Altogether, our observations point to multiple mechanisms of the Ku complex in telomerase regulation and telomere protection in C. albicans, and reveal interesting similarities and differences in the mechanisms of the Ku complex in disparate systems.
异源二聚体 Ku 复合物已被证明参与多种生物体的 DNA 修复和端粒调控。在这里,我们报告了 Ku70 在二倍体真菌病原体白念珠菌中的功能的详细特征。ku70 杂合和纯合缺失突变体具有野生型菌落和细胞形态,对 MMS 或 UV 光不敏感。有趣的是,我们观察到 KU70 基因剂量对端粒长度的复杂影响,KU70/ku70 杂合子表现出略短的端粒,而 ku70 缺失株表现出长而异质的端粒。组合突变体的分析表明,ku70 缺失突变体中端粒的延长主要是由于端粒酶的无调控作用。此外,在缺失突变体中还检测到了高水平的染色体外端粒环,这与异常端粒重组的激活一致。总的来说,我们的观察结果表明 Ku 复合物在白念珠菌中端粒酶调控和端粒保护中的多种机制,并揭示了不同系统中 Ku 复合物在机制上的有趣相似性和差异性。