Role of the homologous recombination genes RAD51 and RAD59 in the resistance of Candida albicans to UV light, radiomimetic and anti-tumor compounds and oxidizing agents.
Role of the homologous recombination genes RAD51 and RAD59 in the resistance of Candida albicans to UV light, radiomimetic and anti-tumor compounds and oxidizing agents.
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DOI：
10.1016/j.fgb.2010.02.007
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发表时间：
2010-05
影响因子：
3
通讯作者：
Larriba, German
中科院分区：
文献类型：
--
作者：
Garcia-Prieto, Fatima;Gomez-Raja, Jonathan;Andaluz, Encarnacion;Calderone, Richard;Larriba, German
我们克隆并鉴定了致病真菌白色念珠菌的 RAD51 和 RAD59 直系同源物。 CaRad51 与其他几种真核生物表现出超过 50% 的同一性，并且具有细菌 RecA 的保守催化结构域。与亲本菌株相比，rad51 无效菌株表现出丝状形态，生长速率降低，并对紫外线、氧化剂和引起双链断裂 (DSB) 的化合物表现出中等敏感性，表明其在 DNA 修复中的作用。相比之下，rad52 null 的细丝百分比更高，生长缺陷更严重，对 DNA 损伤化合物更敏感。 rad59 的无效菌株显示出紫外线敏感表型，但在其余测定中与亲本菌株表现相似。与酿酒酵母相比，白色念珠菌对博莱霉素的抗性要强得多，其各自的同源重组（HR）突变体也是如此。这些结果表明，如酿酒酵母中所述，RAD52 在白色念珠菌 DSB 修复中比 RAD51 发挥更突出的作用，并表明至少存在两种依赖 Rad52 的 HR 途径，一种依赖于 Rad51，一种独立于 Rad51。
We have cloned and characterized the RAD51 and RAD59 orthologues of the pathogenic fungus Candida albicans. CaRad51 exhibited more than 50% identity with several other eukaryotes and the conserved the catalytic domain of a bacterial RecA. As compared to the parental strain, null strains of rad51 exhibited a filamentous morphology, had a decreased grow rate and exhibited a moderate sensitivity to UV light, oxidizing agents, and compounds that cause double-strand breaks (DSB), indicating a role in DNA repair. By comparison, the rad52 null had a higher percentage of filaments, a more severe growth defect and a greater sensitivity to DNA-damaging compounds. Null strains of rad59 showed a UV-sensitive phenotype but behaved similarly to the parental strain in the rest of the assays. As compared to S. cerevisiae, C. albicans was much more resistant to bleomycin and the same was true for their respective homologous recombination (HR) mutants. These results indicate that, as described in S. cerevisiae, RAD52 plays a more prominent role than RAD51 in the repair of DSBs in C. albicans and suggest the existence of at least two Rad52-dependent HR pathways, one dependent and one independent of Rad51.
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