DNA polymerase activity on synthetic N3'→P5' phosphoramidate DNA templates.
Journal
Nucleic acids research
ISSN: 1362-4962
Titre abrégé: Nucleic Acids Res
Pays: England
ID NLM: 0411011
Informations de publication
Date de publication:
26 09 2019
26 09 2019
Historique:
accepted:
01
08
2019
revised:
29
07
2019
received:
22
04
2019
pubmed:
21
8
2019
medline:
21
12
2019
entrez:
21
8
2019
Statut:
ppublish
Résumé
Genetic polymers that could plausibly govern life in the universe might inhabit a broad swath of chemical space. A subset of these genetic systems can exchange information with RNA and DNA and could therefore form the basis for model protocells in the laboratory. N3'→P5' phosphoramidate (NP) DNA is defined by a conservative linkage substitution and has shown promise as a protocellular genetic material, but much remains unknown about its functionality and fidelity due to limited enzymatic tools. Conveniently, we find widespread NP-DNA-dependent DNA polymerase activity among reverse transcriptases, an observation consistent with structural studies of the RNA-like conformation of NP-DNA duplexes. Here, we analyze the consequences of this unnatural template linkage on the kinetics and fidelity of DNA polymerization activity catalyzed by wild-type and variant reverse transcriptases. Template-associated deficits in kinetics and fidelity suggest that even highly conservative template modifications give rise to error-prone DNA polymerase activity. Enzymatic copying of NP-DNA sequences is nevertheless an important step toward the future study and engineering of this synthetic genetic polymer.
Identifiants
pubmed: 31428779
pii: 5552059
doi: 10.1093/nar/gkz707
pmc: PMC6755091
doi:
Substances chimiques
Amides
0
Oligonucleotides
0
Phosphoric Acids
0
RNA
63231-63-0
DNA
9007-49-2
phosphoramidic acid
9Q189608GB
RNA-Directed DNA Polymerase
EC 2.7.7.49
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
8941-8949Subventions
Organisme : CIHR
Pays : Canada
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.
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