Human papillomavirus DNA replication -: Interactions between the viral E1 protein and two subunits of human DNA polymerase α/primase

Human papillomavirus DNA replication -: Interactions between the viral E1 protein and two subunits of human DNA polymerase α/primase
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DOI:
10.1074/jbc.274.5.2696
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发表时间:
1999-01-29
影响因子:
4.8
通讯作者:
Wang, TSF
Wang, TSF
中科院分区:
生物学2区
文献类型:
--
作者:
Conger, KL;Liu, JS;Wang, TSF

文献摘要

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乳多空病毒是研究高等真核生物中DNA复制的有价值的模型,因为它们的DNA复制依赖于宿主因子。在这项研究中,我们研究了人乳头瘤病毒11型(HPV-11)起源识别和起始蛋白E1与人聚合酶α/引物酶之间的相互作用。通过使用各种物理测定,我们表明pol α/引发酶的180-(p180)和70-kDa(p70)亚基与HPV-11 E1相互作用,E1与p180和p70的相互作用在含HPV-11来源质粒的无细胞复制中具有不同的功能,外源性p180抑制HPV-11的E2依赖性和E2非依赖性的无细胞复制,而p70抑制E2依赖性但刺激ES非依赖性复制。我们的实验表明,p70不与E2的物理相互作用,并建议它可能与E2竞争结合E1,E2和p70如何顺序与E1在病毒DNA复制的启动过程中相互作用的模型提出。
Papovaviruses are valuable models for the study of DNA replication in higher eukaryotic organisms, as they depend on host factors for replication of their DNA. In this study we investigate the interactions between the human papillomavirus type 11 (HPV-11) origin recognition and initiator protein E1 and human polymerase alpha/primase (pol alpha/primase) subunits, By using a variety of physical assays, we show that both 180- (p180) and 70-kDa (p70) subunits of pol alpha/primase interact with HPV-11 E1, The interactions of E1 with p180 and p70 are functionally different in cell-free replication of an HPV-11 origin-containing plasmid, Exogenously added p180 inhibits both E2-dependent and E2-independent cell-free replication of HPV-11, whereas p70 inhibits E2-dependent but stimulates ES-independent replication. Our experiments indicate that p70 does not physically interact with E2 and suggest that it may compete with E2 for binding to E1, A model of how E2 and p70 sequentially interact with E1 during initiation of viral DNA replication is proposed.