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首页> 外文期刊>Molecular and Cellular Biology >The Saccharomyces cerevisiae IMP2 gene encodes a transcriptional activator that mediates protection against DNA damage caused by bleomycin and other oxidants.
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The Saccharomyces cerevisiae IMP2 gene encodes a transcriptional activator that mediates protection against DNA damage caused by bleomycin and other oxidants.

机译：酿酒酵母IMP2基因编码转录激活因子，介导针对博来霉素和其他氧化剂引起的DNA损伤的保护作用。

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摘要

Bleomycin belongs to a class of antitumor drugs that damage cellular DNA through the production of free radicals. The molecular basis by which eukaryotic cells provide resistance to the lethal effects of bleomycin is not clear. Using the yeast Saccharomyces cerevisiae as a model with which to study the effect of bleomycin damage on cellular DNA, we isolated several mutants that display hypersensitivity to bleomycin. A DNA clone containing the IMP2 gene that complemented the most sensitive bleomycin mutant was identified. A role for IMP2 in defense against the toxic effects of bleomycin has not been previously reported. imp2 null mutants were constructed and were found to be 15-fold more sensitive to bleomycin than wild-type strains. The imp2 null mutants were also hypersensitive to several oxidants but displayed parental resistance to UV light and methyl methane sulfonate. Exposure of mutants to either bleomycin or hydrogen peroxide resulted in the accumulation of strand breaks in the chromosomal DNA, which remained even after 6 h postchallenge, but not in the wild type. These results suggest that the oxidant hypersensitivity of the imp2 mutant results from a defect in the repair of oxidative DNA lesions. Molecular analysis of IMP2 indicates that it encodes a transcriptional activator that can activate a reporter gene via an acidic domain located at the N terminus. Imp2 lacks a DNA binding motif, but it possesses a C-terminal leucine-rich repeat. With these data taken together, we propose that Imp2 prevents oxidative damage by regulating the expression of genes that are directly required to repair DNA damage.
机译：博来霉素属于一类抗肿瘤药物，通过产生自由基来破坏细胞DNA。真核细胞提供对博来霉素致死作用的抗性的分子基础尚不清楚。使用酵母酿酒酵母作为模型来研究博来霉素损伤对细胞DNA的影响，我们分离了几个对博来霉素表现出超敏性的突变体。鉴定出了一个DNA克隆，该克隆包含与最敏感的博来霉素突变体互补的IMP2基因。以前尚未报道过IMP2在防御博来霉素毒性作用中的作用。构建了imp2无效突变体，发现其对博来霉素的敏感性比野生型菌株高15倍。 imp2无效突变体对几种氧化剂也很敏感，但对紫外线和甲烷磺酸甲酯表现出亲代抵抗性。突变体暴露于博来霉素或过氧化氢会导致染色体DNA中链断裂的积累，即使在攻击后6小时后仍保持断裂，但在野生型中则不存在。这些结果表明，imp2突变体的氧化剂超敏性是由氧化性DNA损伤修复中的缺陷引起的。 IMP2的分子分析表明，它编码一个转录激活因子，该激活因子可以通过位于N末端的酸性域激活报告基因。 Imp2缺乏DNA结合基序，但具有C端富含亮氨酸的重复序列。结合这些数据，我们提出Imp2通过调节直接修复DNA损伤所需基因的表达来防止氧化损伤。

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