RETROVIRAL INTEGRATION - STRUCTURE OF THE INITIAL COVALENT PRODUCT AND ITS PRECURSOR, AND A ROLE FOR THE VIRAL IN PROTEIN
RETROVIRAL INTEGRATION - STRUCTURE OF THE INITIAL COVALENT PRODUCT AND ITS PRECURSOR, AND A ROLE FOR THE VIRAL IN PROTEIN
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DOI：
10.1073/pnas.86.8.2525
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发表时间：
1989-04-01
影响因子：
11.1
通讯作者：
BISHOP, JM
中科院分区：
文献类型：
--
作者：
BROWN, PO;BOWERMAN, B;BISHOP, JM
逆转录病毒生命周期中的一个重要步骤是将病毒基因组的 DNA 副本整合到宿主细胞染色体中。我们分析了体外逆转录病毒整合反应的初始共价产物的结构，并确定了鼠白血病病毒（MLV）感染细胞体内存在的未整合线性病毒DNA分子末端的结构。我们的结果得出以下结论：（i）病毒 DNA 的环化在整合中不起任何作用。整合的 MLV 原病毒的直接前体是线性分子。 (ii) 整合反应的第一步可能是切割，从病毒 DNA 的每个 3'' 末端去除末端 2 个碱基。这种切割取决于病毒编码的蛋白质 IN，此前已被证明是整合所必需的。 (iii) 将所得病毒 3'' 末端连接至靶 DNA 以形成初始重组中间体。
An essential step in the life cycle of a retrovirus is the integration of a DNA copy of the viral genome into a host cell chromosome. We have analyzed the structure of the initial covalent product of an in vitro retroviral integration reaction and determined the structure of the ends of the unintegrated linear viral DNA molecules present in vivo in cells infected with murine leukemia virus (MLV). Our results lead to the following conclusions: (i) Circularization of vrial DNA plays no role in integration. The direct precursor to the integrated MLV provirus is a linear molecule. (ii) The initial step in the integration reaction is probably a cleavage that removes the terminal 2 bases from each 3'' end of the viral DNA. This cleavage depends on a virally encoded protein, IN, that has previously been shown gentically to be required for integration. (iii) The resulting viral 3'' ends are joined to target DNA to form the initial recombination intermediate.