Department of Developmental, Molecular and Chemical Biology, Tufts University School of Medicine, 136 Harrison Avenue, Boston, MA, 02111, USA.
Center for Computational and Integrative Biology, Simches Research Center, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA, 02114, USA.
Virology. 2020 Apr;543:27-33. doi: 10.1016/j.virol.2020.01.013. Epub 2020 Jan 29.
When purified from persistent infections, the genomes of most human polyomaviruses contain single enhancers. However, when isolated from productively infected cells from immunocompromised individuals, the genomes of several polyomaviruses contain duplicated enhancers that promote a number of polyoma-based diseases. The mechanism(s) that gives rise to the duplicated enhancers in the polyomaviruses is, however, not known. Herein we propose a model for the duplication of the enhancers that is based on recent advances in our understanding of; 1) the initiation of polyomavirus DNA replication, 2) the formation of long flaps via displacement synthesis and 3) the subsequent generation of duplicated enhancers via double stranded break repair. Finally, we discuss the possibility that the polyomavirus based replication dependent enhancer duplication model may be relevant to the enhancer-associated rearrangements detected in human genomes that are associated with various diseases, including cancers.
当从持续感染中纯化时，大多数人类多瘤病毒的基因组仅包含一个增强子。然而，当从免疫功能低下个体的感染细胞中分离时，几种多瘤病毒的基因组包含重复的增强子，这些增强子促进了多种基于多瘤病毒的疾病。然而，导致多瘤病毒中重复增强子的机制尚不清楚。本文中，我们提出了一种基于我们对以下方面的最新理解的增强子复制模型：1）多瘤病毒 DNA 复制的起始，2）通过置换合成形成长的发夹结构，以及 3）通过双链断裂修复随后产生重复的增强子。最后，我们讨论了基于多瘤病毒的复制依赖性增强子复制模型是否与与各种疾病（包括癌症）相关的人类基因组中检测到的增强子相关重排相关的可能性。
