The Candida albicans Ku70 modulates telomere length and structure by regulating both telomerase and recombination.

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复合物已被证明在多种生物中参与DNA修复和端粒调控。在此我们详细报道Ku70在二倍体真菌病原体白色念珠菌中的功能特性。ku70杂合和纯合缺失突变体都具有野生型的菌落和细胞形态，并且对甲基磺酸甲酯（MMS）或紫外线不敏感。有趣的是，我们观察到KU70基因剂量对端粒长度有复杂的影响，KU70/ku70杂合子的端粒稍短，而ku70缺失株的端粒长且具有异质性。对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不受调控作用。此外，在缺失突变体中检测到染色体外端粒环水平升高，这与异常端粒重组的激活相符。总之，我们的观察结果表明Ku复合物在白色念珠菌的端粒酶调控和端粒保护中存在多种机制，并揭示了Ku复合物在不同系统中的机制存在有趣的相似性和差异性。