Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo
Uncoupling of leading- and lagging-strand DNA replication during lesion bypass in vivo
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DOI：
10.1126/science.1083964
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发表时间：
2003-05-23
期刊：
影响因子：
56.9
通讯作者：
Fuchs, RP
中科院分区：
文献类型：
--
作者：
Pagès, V;Fuchs, RP
许多病原体攻击DNA，形成损害正常复制的病变。特殊的DNA聚合酶短暂地取代复制聚合酶并复制过去的病变，从而产生突变，这是癌症的主要起始原因。我们在大肠杆菌中监测了两条DNA分子链的复制动力学，这些DNA分子链在前导链或后链中含有单个复制块。尽管前导链中有阻滞，滞后链的合成继续进行，这意味着同步链合成的短暂解耦。通过病变的复制需要专门的DNA聚合酶，并且在两条链中以相似的动力学和效率实现。
Numerous agents attack DNA, forming lesions that impair normal replication. Specialized DNA polymerases transiently replace the replicative polymerase and copy past lesions, thus generating mutations, the major initiating cause of cancer. We monitored, in Escherichia coli, the kinetics of replication of both strands of DNA molecules containing a single replication block in either the leading or lagging strand. Despite a block in the leading strand, lagging-strand synthesis proceeded further, implying transient uncoupling of concurrent strand synthesis. Replication through the lesion requires specialized DNA polymerases and is achieved with similar kinetics and efficiencies in both strands.