Mononucleotide repeat expansions with non-natural polymerase substrates

Abstract Replicative strand slippage is a biological phenomenon, ubiquitous among different organisms. However, slippage events are also relevant to non-natural replication models utilizing synthetic polymerase substrates. Strand slippage may notably affect the outcome of the primer extension reacti...

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Autores principales: Alexander V. Chudinov, Vadim A. Vasiliskov, Viktoriya E. Kuznetsova, Sergey A. Lapa, Natalia A. Kolganova, Edward N. Timofeev
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/7b73fccda1b24e75804200257fc598d1
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Sumario:Abstract Replicative strand slippage is a biological phenomenon, ubiquitous among different organisms. However, slippage events are also relevant to non-natural replication models utilizing synthetic polymerase substrates. Strand slippage may notably affect the outcome of the primer extension reaction with repetitive templates in the presence of non-natural nucleoside triphosphates. In the current paper, we studied the ability of Taq, Vent (exo-), and Deep Vent (exo-) polymerases to produce truncated, full size, or expanded modified strands utilizing non-natural 2′-deoxyuridine nucleotide analogues and different variants of the homopolymer template. Our data suggest that the slippage of the primer strand is dependent on the duplex fluttering, incorporation efficiency for a particular polymerase-dNTP pair, rate of non-templated base addition, and presence of competing nucleotides.