Requirement for uracil-DNA glycosylase during the transition to late-phase cytomegalovirus DNA replication
Requirement for uracil-DNA glycosylase during the transition to late-phase cytomegalovirus DNA replication
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DOI：
10.1128/jvi.75.16.7592-7601.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Mocarski, ES
中科院分区：
文献类型：
--
作者：
Courcelle, CT;Courcelle, J;Mocarski, ES
巨细胞病毒基因UL114是哺乳动物尿嘧啶-DNA糖基酶(UNG)的同源基因，是病毒DNA高效复制所必需的。在静止的成纤维细胞中，UNG突变病毒复制延迟48h，并跟随病毒诱导的细胞UNG表达。相比之下，突变病毒的复制在活跃生长的表达宿主细胞UNG的成纤维细胞中毫不迟疑地进行。在缺乏病毒或宿主细胞UNG表达的情况下，突变病毒无法进行以快速DNA扩增为特征的晚期DNA复制。这些数据表明，在野生型病毒DNA复制过程中早期加入的尿嘧啶必须在后期扩增和封装到子代病毒粒子之前被病毒或宿主UNG移除。尿嘧啶掺入和切除的过程可能会导致链断裂，从而促进从早期复制到晚期扩增的过渡。
Cytomegalovirus gene UL114, a homolog of mammalian uracil-DNA glycosylase (UNG), is required for efficient viral DNA replication. In quiescent fibroblasts, UNG mutant virus replication is delayed for 48 h and follows the virus-induced expression of cellular UNG. In contrast, mutant virus replication proceeds without delay in actively growing fibroblasts that express host cell UNG. In the absence of viral or host cell UNG expression, mutant virus fails to proceed to late-phase DNA replication, characterized by rapid DNA amplification. The data suggest that uracil incorporated early during wild-type viral DNA replication must be removed by virus or host UNG prior to late-phase amplification and encapsidation into progeny virions. The process of uracil incorporation and excision may introduce strand breaks to facilitate the transition from early-phase replication to late-phase amplification.