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Enzyme‐Free Replication with Two or Four Bases
Angewandte Chemie International Edition ( IF 16.1 ) Pub Date : 2018-06-19 , DOI: 10.1002/anie.201803074
Elena Hänle 1 , Clemens Richert 1
Affiliation  

All known forms of life encode their genetic information in a sequence of bases of a genetic polymer and produce copies through replication. How this process started before polymerase enzymes had evolved is unclear. Enzyme‐free copying of short stretches of DNA or RNA has been demonstrated using activated nucleotides, but not replication. We have developed a method for enzyme‐free replication. It involves extension with reversible termination, enzyme‐free ligation, and strand capture. We monitored nucleotide incorporation for a full helical turn of DNA, during both a first and a second round of copying, by using mass spectrometry. With all four bases (A/C/G/T), an “error catastrophe” occurred, with the correct sequence being “overwhelmed” by incorrect ones. When only C and G were used, approximately half of the daughter strands had the mass of the correct sequence after 20 copying steps. We conclude that enzyme‐free replication is more likely to be successful with just the two strongly pairing bases than with all four bases of the genetic alphabet.

中文翻译:

具有两个或四个碱基的无酶复制

所有已知的生命形式都以遗传聚合物的碱基序列编码其遗传信息,并通过复制产生拷贝。目前尚不清楚该过程如何在聚合酶进化之前开始。已经证明了使用活化的核苷酸而不是复制可以短片段DNA或RNA进行无酶复制。我们已经开发出一种无酶复制的方法。它涉及可逆终止,无酶连接和链捕获的延伸。在第一轮和第二轮复制过程中,我们通过使用质谱法监测了核苷酸掺入过程中DNA的完整螺旋转角。在所有四个基地(A / C / G / T)下,发生了“错误灾难”,正确的顺序被不正确的顺序“淹没”。当仅使用C和G时,20个复制步骤后,大约一半的子链具有正确序列的质量。我们得出结论,与遗传字母的所有四个碱基相比,仅使用两个强配对碱基,无酶复制更有可能成功。
更新日期:2018-06-19
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