Wu H, Ceccarelli D F, Frappier L
Department of Medical Genetics and Microbiology, University of Toronto, Ontario, Canada.
EMBO Rep. 2000 Aug;1(2):140-4. doi: 10.1093/embo-reports/kvd026.
Latent Epstein-Barr virus (EBV) genomes are maintained in human cells as low copy number episomes that are thought to be partitioned by attachment to the cellular mitotic chromosomes through the viral EBNA1 protein. We have identified a human protein, EBP2, which interacts with the EBNA1 sequences that govern EBV partitioning. Here we show that, in mitosis, EBP2 localizes to the condensed cellular chromosomes producing a staining pattern that is indistinguishable from that of EBNA1. The localization of EBNA1 proteins with mutations in the EBP2 binding region was also examined. An EBNA1 mutant (delta325-376) disrupted for EBP2 binding and segregation function was nuclear but failed to attach to the cellular chromosomes in mitosis. Our results indicate that amino acids 325-376 mediate the binding of EBNA1 to mitotic chromosomes and strongly suggest that EBNA1 mediates EBV segregation by attaching to EBP2 on the cellular mitotic chromosomes.
潜伏的爱泼斯坦-巴尔病毒（EBV）基因组以低拷贝数附加体的形式存在于人类细胞中，人们认为这些附加体通过病毒EBNA1蛋白附着于细胞有丝分裂染色体上而得以分配。我们鉴定出一种人类蛋白EBP2，它与控制EBV分配的EBNA1序列相互作用。在此我们表明，在有丝分裂过程中，EBP2定位于浓缩的细胞染色体上，产生的染色模式与EBNA1的染色模式无法区分。我们还研究了EBP2结合区域发生突变的EBNA1蛋白的定位情况。一个因EBP2结合和分离功能受损的EBNA1突变体（delta325 - 376）位于细胞核中，但在有丝分裂过程中未能附着于细胞染色体上。我们的结果表明，氨基酸325 - 376介导EBNA1与有丝分裂染色体的结合，并强烈提示EBNA1通过附着于细胞有丝分裂染色体上的EBP2来介导EBV的分离。
