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UBA52 在职工和细胞模型中在六价暴露下调解核糖体DNA稳定性

Huadong Xu¹, Fan Wu², Chuyan Zhang¹

¹School of Public Health, Hangzhou Medical College, Hangzhou, Zhejiang 310013, China.

Ecotoxicology and environmental safety

|March 16, 2025

概括

六价 (Cr(VI)) 暴露会增加基因组的不稳定性. 乌比基A-52核糖体蛋白融合产物1 (UBA52) 在Cr(VI) 压力下有助于稳定核糖体DNA复制数 (rDNA CN),为细胞反应提供了洞察力.

科学领域:

环境健康环境健康
基因组学就是基因组学.
分子生物学分子生物学

背景情况:

暴露于六价 (Cr(VI)) 是与基因组不稳定性相关的重大职业危险.
之前的研究表明,Cr (VI) 暴露可以诱导DNA拷贝数 (CN) 的变化.

研究的目的:

为了研究Ubiquitin A-52核糖体蛋白融合产品1 (UBA52) 在Cr(VI) 暴露期间维持核糖体DNA复制数 (rDNA CN) 稳定性的作用.
分析Cr (VI) 暴露的工人和体外细胞模型中的分子反应.

主要方法:

分析血液中的Cr水平,γH2AX表达,rDNA CN和UBA52表达在Cr (VI) 暴露的工人和对照中.
斯皮尔曼和回归分析以确定Cr水平,UBA52表达和rDNA CN.之间的相关性.
使用BEAS-2BR和HeLa细胞进行体外研究,以评估Cr(VI) 对UBA52和rDNA CN的影响,包括UBA52敲击实验.

主要成果:

暴露于Cr (VI) 的个体表现出高血Cr,高GH2AX,高rDNACN,以及高调的UBA52mRNA和蛋白质.
在Cr水平和UBA52表达之间,以及UBA52表达和rDNA CN.之间发现了正相关性.
在体外,Cr(VI) 调高了UBA52,UBA52的降低导致了rDNA CN的不稳定.

结论:

UBA52在稳定rDNA CN对抗Cr(VI) 诱导的基因组压力方面发挥着至关重要的作用.
这些发现阐明了一个关键的分子机制,以应对环境中的Cr (VI) 暴露.

关键词:

造成的DNA损伤是DNA损伤.基因组不稳定性基因组不稳定性六价的六价是一种有关RDNA复制号码的编号.在UBA52中,UBA52是UBA52.

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