RAD6 gene is involved in heat shock induction of bleomycin resistance in Saccharomyces cerevisiae

RAD6 gene is involved in heat shock induction of bleomycin resistance in Saccharomyces cerevisiae
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RAD6基因参与热激诱导酿酒酵母博莱霉素抗性

DOI:
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发表时间:
2005
影响因子:
2.8
通讯作者:
E. Nunes
E. Nunes
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
D. Keszenman;E. Candreva;Ana G. Sánchez;E. Nunes

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细胞通过激活几种称为应激反应的防御机制来应对环境和内源性挑战,例如高温、活性氧、DNA损伤和营养饥饿。一个重要的特征是不同压力反应之间的重叠,这至少部分地导致了交叉保护现象。我们先前证明,热休克(HS)预处理诱导野生型酿酒酵母对药物博莱霉素(BLM)的致死和致突变作用的抗性。在DNA水平上,HS导致BLM诱导的DNA损伤的更有效修复。在本研究中,我们研究了HS诱导的BLM抗性的机制。由于RAD6基因参与泛素系统和DNA修复,我们分析了HS对S.rad6 Δ(ubc2)突变株BLM致死性的影响。酿酒。突变体对BLM的致死作用比野生型酵母更敏感,HS对突变体中BLM的致死作用没有影响。细胞增殖动力学分析表明,在野生型酵母中观察到的HS诱导的细胞周期延迟在rad6Δ突变菌株中不存在。BLM处理损害突变体细胞增殖,和HS对延迟的细胞动力学的突变体没有影响。此外,BLM损伤的染色体的脉冲场电泳表明,在不含BLM的营养培养基中孵育24小时后,突变体的损伤几乎没有恢复,HS对恢复的影响很小。这些数据表明,RAD6基因参与了在同基因野生型菌株中观察到的HS诱导的BLM抗性。Environ.摩尔诱变剂,2005.© 2004 Wiley利斯公司
Cells react to environmental and endogenous challenges such as high temperature, reactive oxygen species, DNA damage, and nutrient starvation by activating several defense mechanisms known as stress responses. An important feature is the overlap between different stress responses that contributes at least in part to the phenomenon of cross‐protection. We previously demonstrated that pretreatment with a heat shock (HS) induces resistance to the lethal and mutagenic effects of the antineoplastic drug Bleomycin (BLM) in wild‐type Saccharomyces cerevisiae. At the DNA level, the HS resulted in more efficient repair of BLM‐induced DNA damage. In the present study, we have investigated the mechanisms involved in this HS‐induced BLM resistance. Since the RAD6 gene is involved in the ubiquitin system and DNA repair, we analyzed the effects of HS on the lethality of BLM in a rad6Δ (ubc2) mutant strain of S. cerevisiae. The rad6Δ mutant was more sensitive to the lethal effects of BLM than wild‐type yeast and HS had no effect on the lethality of BLM in the mutant. Analysis of cell proliferation kinetics indicated that the HS‐induced cell cycle delay observed in the wild‐type yeast was absent in the rad6Δ mutant strain. BLM treatment impaired mutant cell proliferation, and HS had no effect on the delayed cell kinetics of the mutant. In addition, pulsed‐field electrophoresis of chromosomes damaged by BLM indicated that there was very little recovery from damage in the mutant after 24 hr of incubation in BLM‐free nutrient medium, and that HS had little effect on the recovery. These data indicate that the RAD6 gene is involved in the HS‐induced BLM resistance observed in the isogenic wild‐type strain. Environ. Mol. Mutagen., 2005. © 2004 Wiley‐Liss, Inc.
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