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首页> 外文期刊>Cell Division >The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress
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The yeast mitogen-activated protein kinase Slt2 is involved in the cellular response to genotoxic stress

机译：酵母促分裂原激活蛋白激酶Slt2参与细胞对遗传毒性胁迫的反应

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Background The maintenance of genomic integrity is essential for cell viability. Complex signalling pathways (DNA integrity checkpoints) mediate the response to genotoxic stresses. Identifying new functions involved in the cellular response to DNA-damage is crucial. The Saccharomyces cerevisiae SLT2 gene encodes a member of the mitogen-activated protein kinase (MAPK) cascade whose main function is the maintenance of the cell wall integrity. However, different observations suggest that SLT2 may also have a role related to DNA metabolism. Results This work consisted in a comprehensive study to connect the Slt2 protein to genome integrity maintenance in response to genotoxic stresses. The slt2 mutant strain was hypersensitive to a variety of genotoxic treatments, including incubation with hydroxyurea (HU), methylmetanosulfonate (MMS), phleomycin or UV irradiation. Furthermore, Slt2 was activated by all these treatments, which suggests that Slt2 plays a central role in the cellular response to genotoxic stresses. Activation of Slt2 was not dependent on the DNA integrity checkpoint. For MMS and UV, Slt2 activation required progression through the cell cycle. In contrast, HU also activated Slt2 in nocodazol-arrested cells, which suggests that Slt2 may respond to dNTP pools alterations. However, neither the protein level of the distinct ribonucleotide reductase subunits nor the dNTP pools were affected in a slt2 mutant strain. An analysis of the checkpoint function revealed that Slt2 was not required for either cell cycle arrest or the activation of the Rad53 checkpoint kinase in response to DNA damage. However, slt2 mutant cells showed an elongated bud and partially impaired Swe1 degradation after replicative stress, indicating that Slt2 could contribute, in parallel with Rad53, to bud morphogenesis control after genotoxic stresses. Conclusions Slt2 is activated by several genotoxic treatments and is required to properly cope with DNA damage. Slt2 function is important for bud morphogenesis and optimal Swe1 degradation under replicative stress. The MAPK Slt2 appears as a new player in the cellular response to genotoxic stresses.
机译：背景技术维持基因组完整性对于细胞活力至关重要。复杂的信号通路（DNA完整性检查点）介导了对遗传毒性胁迫的响应。识别涉及细胞对DNA损伤的新功能至关重要。酿酒酵母SLT2基因编码有丝分裂原激活的蛋白激酶（MAPK）级联的成员，其主要功能是维持细胞壁完整性。但是，不同的观察结果表明SLT2也可能与DNA代谢有关。结果这项工作包括一项全面的研究，以将Slt2蛋白连接到基因组完整性维护中，以应对遗传毒性胁迫。 slt2突变株对多种遗传毒性治疗均敏感，包括与羟基脲（HU），甲基磺酸甲酯（MMS），鞘霉素或紫外线照射的孵育。此外，所有这些处理均激活了Slt2，这表明Slt2在细胞对遗传毒性胁迫的反应中起着核心作用。 Slt2的激活不依赖于DNA完整性检查点。对于MMS和UV，Slt2激活需要整个细胞周期进行。相比之下，HU还激活了去甲多达唑停滞的细胞中的Slt2，这表明Slt2可能对dNTP库的变化有反应。但是，在slt2突变株中，独特的核糖核苷酸还原酶亚基的蛋白质水平和dNTP库均不受影响。对检查点功能的分析表明，细胞周期停滞或响应DNA损伤的Rad53检查点激酶的激活均不需要Slt2。但是，slt2突变细胞在复制胁迫后显示出伸长的芽并部分损害了Swe1的降解，这表明在遗传毒性胁迫后，Slt2可以与Rad53平行地参与芽形态控制。结论Slt2被多种遗传毒性处理激活，是正确应对DNA损伤所必需的。 Slt2功能对于复制形态下的芽形态发生和最佳Swe1降解很重要。 MAPK Slt2似乎是细胞对遗传毒性应激的新反应。

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