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首页> 外文期刊>PLoS Genetics >Histone H4 dosage modulates DNA damage response in the pathogenic yeast Candida glabrata via homologous recombination pathway
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Histone H4 dosage modulates DNA damage response in the pathogenic yeast Candida glabrata via homologous recombination pathway

机译：组蛋白H4剂量通过同源重组途径调节致病酵母中的DNA损伤响应<斜度> Candida Glabrata

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摘要

Candida glabrata , a nosocomial fungal bloodstream pathogen, causes significant morbidity and mortality in hospitals worldwide. The ability to replicate in macrophages and survive a high level of oxidative stress contributes to its virulence in the mammalian host. However, the role of DNA repair and recombination mechanisms in its pathobiology is still being discovered. Here, we have characterized the response of C . glabrata to the methyl methanesulfonate (MMS)-induced DNA damage. We found that the MMS exposure triggered a significant downregulation of histone H4 transcript and protein levels, and that, the damaged DNA was repaired by the homologous recombination (HR) pathway. Consistently, the reduced H4 gene dosage was associated with increased HR frequency and elevated resistance to MMS. The genetic analysis found CgRad52, a DNA strand exchange-promoter protein of the HR system, to be essential for this MMS resistance. Further, the tandem-affinity purification and mass spectrometry analysis revealed a substantially smaller interactome of H4 in MMS-treated cells. Among 23 identified proteins, we found the WD40-repeat protein CgCmr1 to interact genetically and physically with H4, and regulate H4 levels, HR pathway and MMS stress survival. Controlling H4 levels tightly is therefore a regulatory mechanism to survive MMS stress in C . glabrata .
机译：Candida Glabrata是一种医院真菌血流病原体，在全世界的医院引起显着的发病率和死亡率。在巨噬细胞中复制并存活高水平氧化应激的能力有助于哺乳动物宿主的毒力。然而，仍在发现DNA修复和重组机制在其病理学中的作用。在这里，我们表征了C的响应。 Glabrata甲磺酸甲酯（MMS）诱导的DNA损伤。我们发现MMS暴露引发了组蛋白H4转录物和蛋白质水平的显着下调，并且通过同源重组（HR）途径修复了受损的DNA。始终如一地，降低的H4基因剂量与HR频率升高相关，升高到MMS。遗传分析发现Cgrad52，HR系统的DNA链交换促进剂蛋白，对该凸肌电阻是必不可少的。此外，串联 - 亲和纯化和质谱分析显示了在MMS处理细胞中的基本上较小的H4偶联。在23个鉴定的蛋白质中，我们发现WD40重复蛋白CGCMR1与H4的遗传和物理相互作用，并调节H4水平，HR途径和MMS应激存活。因此，控制H4水平因此是在C中存活MMS应激的调节机制。 Glabrata。

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