The NS1 protein of the autonomous parvovirus minute virus of mice blocks cellular DNA replication: A consequence of lesions to the chromatin?
The NS1 protein of the autonomous parvovirus minute virus of mice blocks cellular DNA replication: A consequence of lesions to the chromatin?
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DOI：
10.1128/jvi.71.7.5323-5329.1997
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发表时间：
1997-07-01
影响因子：
5.4
通讯作者：
CailletFauquet, P
中科院分区：
文献类型：
--
作者：
DeBeeck, AO;CailletFauquet, P
小鼠自主细小病毒微小病毒的非结构蛋白NS1干扰细胞分裂，并可导致细胞死亡，具体取决于细胞转化状态。在受侵染后，Ns1蛋白的合成在S期大量启动。在这篇文章中，我们展示了小鼠感染细胞的微小病毒在这一阶段积累。为了研究Ns1基因的积累与S期阻滞之间的联系，我们使用了稳定表达的细胞，其中Ns1基因的表达受糖皮质激素诱导的启动子(小鼠乳腺肿瘤病毒的长端重复序列)的控制，Ns1基因的表达干扰了细胞的DNA复制，从而使细胞周期停止在S期，Ns1基因的表达也诱导了细胞染色质的缺口。原位缺口翻译实验检测到，NICK发生在细胞周期扰动的几个小时之前，由于细胞周期停滞是DNA损伤的常见结果，我们认为NS1通过诱导细胞染色质损伤来发挥其细胞抑制活性。
The nonstructural protein NS1 of the autonomous parvovirus minute virus of mice interferes with cell division and can cause cell death, depending on the cell transformation state. Upon infection, the synthesis of NS1 protein is massively initiated during S phase. In this article, we show that minute virus of mice-infected cells accumulate in this phase. To investigate the link between NS1 accumulation and S-phase arrest, we have used stably transfected cells in which NS1 expression is under the control of a glucocorticoid-inducible promoter (the long terminal repeat of mouse mammary tumor virus), NS1 expression interferes with cell DNA replication, and consequently, the cell cycle stops in S phase, NS1 expression also induces nicks in the cell chromatin, as detected by an in situ nick translation assay, The nicks are observed several hours before any cell cycle perturbation, As cell cycle arrest is a common consequence of DNA damage, we propose that NS1 exerts its cytostatic activity by inducing lesions in cell chromatin.