Enzyme-Free Replication with Two or Four Bases

Angewandte Chemie
Elena Hänle, Clemens Richert

Abstract

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.

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Citations

Sep 11, 2019·Molecular Biology and Evolution·Andrew S TupperPaul G Higgs
Feb 16, 2020·Journal of Molecular Evolution·David A LiberlesAndrew Storfer
May 20, 2020·Nucleic Acids Research·Daniel DuzdevichJack W Szostak
Feb 23, 2020·Frontiers in Chemistry·Samuel Núñez-Pertíñez, Thomas R Wilks
Nov 9, 2019·ELife·Lijun ZhouJack W Szostak
Aug 8, 2018·Nucleic Acids Research·Tanja J Walter, Clemens Richert
Mar 15, 2019·Nucleic Acids Research·Marilyne SossonClemens Richert
Dec 13, 2018·Nature Communications·Clemens Richert
Mar 5, 2021·Bio-protocol·Derek K O'FlahertyJack W Szostak
Jun 11, 2019·Journal of the American Chemical Society·Derek K O'FlahertyJack W Szostak
Sep 25, 2021·Chemistry : a European Journal·Jianyang HanClemens Richert

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