Li T, Nicolaou K C
Department of Chemistry, Scripps Research Institute, La Jolla, California 92037.
Nature. 1994 May 19;369(6477):218-21. doi: 10.1038/369218a0.
Molecular replication, a fundamental process of life, has in recent years been the subject of laboratory investigations using simple chemical systems. Whereas the work of Rebek's group has focused on molecular architectures not known in living systems, self-replicating and template-based self-assembling systems based on nucleotides are regarded as potential models for exploring the evolution of replicating systems on the early Earth. Previous replicating oligonucleotides have been of the single-stranded, self-complementary type: small oligonucleotide fragments are assembled on a pre-existing template and linked to form an exact copy of the template. This process cannot easily be reiterated, however, because of the strong binding of the newly formed strand to the original template. Furthermore, DNA replication in living systems operates by complementarity rather than self-complementarity--each newly assembled strand is complementary to, rather than identical to, its template--and the replication process starts and finishes with double helices. Here we report the self-replication of palindromic (symmetrical) duplex DNA-like oligonucleotides, 24 monomers long, in the absence of enzymes by means of a cycle that transfers information from template to copy and is potentially capable of extension to include non-symmetrical sequences, selection and mutation. Replication proceeds by a chemical process involving the formation of an intermediate triplex structure, and is sequence-selective in the sense that mismatches impair its efficiency. These results indicate that DNA-like double-helical molecules can replicate without assistance from proteins, a finding that may be relevant both to the appearance of replicating systems on the early Earth and to the development of new approaches to DNA amplification.
分子复制是生命的一个基本过程，近年来一直是使用简单化学系统进行实验室研究的主题。虽然雷贝克小组的工作重点是生命系统中未知的分子结构，但基于核苷酸的自我复制和基于模板的自我组装系统被视为探索早期地球上复制系统进化的潜在模型。以前的复制寡核苷酸是单链、自我互补型的：小的寡核苷酸片段在预先存在的模板上组装并连接起来，形成模板的精确拷贝。然而，由于新形成的链与原始模板的强烈结合，这个过程不容易重复。此外，生命系统中的DNA复制是通过互补性而不是自我互补性进行的——每条新组装的链与其模板互补，而不是相同——并且复制过程以双螺旋开始和结束。在这里，我们报告了24个单体长的回文（对称）双链DNA样寡核苷酸在没有酶的情况下通过一个将信息从模板转移到拷贝的循环进行自我复制，并且有可能扩展到包括非对称序列、选择和突变。复制通过一个涉及形成中间三链结构的化学过程进行，并且在错配会损害其效率的意义上是序列选择性的。这些结果表明，类DNA双螺旋分子可以在没有蛋白质帮助的情况下复制，这一发现可能与早期地球上复制系统的出现以及DNA扩增新方法的发展都有关。
