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
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7b73fccda1b24e75804200257fc598d1
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spelling	oai:doaj.org-article:7b73fccda1b24e75804200257fc598d12021-12-02T13:24:37ZMononucleotide repeat expansions with non-natural polymerase substrates10.1038/s41598-021-82150-22045-2322https://doaj.org/article/7b73fccda1b24e75804200257fc598d12021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82150-2https://doaj.org/toc/2045-2322Abstract 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.Alexander V. ChudinovVadim A. VasiliskovViktoriya E. KuznetsovaSergey A. LapaNatalia A. KolganovaEdward N. TimofeevNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-7 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Alexander V. Chudinov Vadim A. Vasiliskov Viktoriya E. Kuznetsova Sergey A. Lapa Natalia A. Kolganova Edward N. Timofeev Mononucleotide repeat expansions with non-natural polymerase substrates
description	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.
format	article
author	Alexander V. Chudinov Vadim A. Vasiliskov Viktoriya E. Kuznetsova Sergey A. Lapa Natalia A. Kolganova Edward N. Timofeev
author_facet	Alexander V. Chudinov Vadim A. Vasiliskov Viktoriya E. Kuznetsova Sergey A. Lapa Natalia A. Kolganova Edward N. Timofeev
author_sort	Alexander V. Chudinov
title	Mononucleotide repeat expansions with non-natural polymerase substrates
title_short	Mononucleotide repeat expansions with non-natural polymerase substrates
title_full	Mononucleotide repeat expansions with non-natural polymerase substrates
title_fullStr	Mononucleotide repeat expansions with non-natural polymerase substrates
title_full_unstemmed	Mononucleotide repeat expansions with non-natural polymerase substrates
title_sort	mononucleotide repeat expansions with non-natural polymerase substrates
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/7b73fccda1b24e75804200257fc598d1
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Mononucleotide repeat expansions with non-natural polymerase substrates

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