Involvement of human small fragment nuclease in the resistance of human cells to UV-C-induced cell death

Involvement of human small fragment nuclease in the resistance of human cells to UV-C-induced cell death
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DOI:
10.1562/2004-01-21-ra-051.1
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发表时间:
2004-09-01
影响因子:
3.3
通讯作者:
Suzuki, N
Suzuki, N
中科院分区:
生物学3区
文献类型:
--
作者:
Ito, S;Kita, K;Suzuki, N

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人小片段核酸酶(Sfn)是一种能降解单链DNA和RNA的细胞蛋白。然而,Sfn在细胞对各种应激源如UV-C(主要是254 nm波长的紫外线)的反应中的生物学作用仍不清楚。我们已经研究了人类SFN基因表达的调节是否影响细胞对UV-C诱导的细胞死亡的存活能力,分析了用SFN信使RNA(mRNA)特异性的短双链RNA(siRNA)处理的UV-C敏感的人类RSa细胞中的集落存活能力。与对照siRNA处理的细胞相比,siRNA处理的RSa细胞中SFN mRNA的表达水平降低至约15%。与对照组相比,经siRNA处理的RSa细胞在UV-C照射后集落存活率降低,caspase-3活性升高。此外,与对照siRNA处理的RSa细胞相比,siRNA处理的RSa细胞中的环丁烷嘧啶二聚体(CPD)的去除能力降低。对照siRNA处理的RSa细胞和模拟处理的RSa细胞在UV-C照射后的殖民地存活率和CPD去除能力没有差异。这些结果表明,SFN的表达参与抵抗RSa细胞UV-C诱导的细胞死亡,通过它在DNA修复过程中发挥的作用。
Human small fragment nuclease (Sfn) is one of the cellular proteins that were reported to degrade small, single-stranded DNA and RNA. However, the biological role of Sfn in cellular response to various stressors such as UV-C (mainly 254 nm wavelength ultraviolet ray) remains unclear. We have examined whether modulation of human SFN gene expression affects cell survival capacity against UV-C-induced cell death, analyzing colony survival ability in UV-C-sensitive human RSa cells treated with short double-stranded RNA (siRNA) specific for SFN messenger RNA (mRNA). The expression levels of SFN mRNA in the siRNA-treated RSa cells decreased to about 15% compared with those in the control siRNA-treated cells. The siRNA-treated RSa cells showed lower colony survival and higher activity of caspase-3 after UV-C irradiation than the control siRNA-treated RSa cells. Furthermore, the removal capacity of cyclobutane pyrimidine dimers (CPD) in the siRNA-treated RSa cells decreased compared with the control siRNA-treated RSa cells. There was no difference in the colony survival and CPD removal capacity after UV-C irradiation between the control siRNA-treated RSa cells and mock-treated RSa cells. These results suggest that SFN expression is involved in resistance of RSa cells to UV-C-induced cell death through the roles it plays in the DNA repair process.