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Recent progress in dissecting molecular recognition by DNA polymerases with non-native substrates.

ABSTRACT: DNA polymerases must discriminate the correct Watson-Crick base pair-forming deoxynucleoside triphosphate (dNTP) substrate from three other dNTPs and additional triphosphates found in the cell. The rarity of misincorporations in vivo, then, belies the high tolerance for dNTP analogs observed in vitro. Advances over the last 10 years in single-molecule fluorescence and electronic detection of dNTP analog incorporation enable exploration of the mechanism and limits to base discrimination by DNA polymerases. Such studies reveal transient motions of DNA polymerase during substrate recognition and mutagenesis in the context of erroneous dNTP incorporation that can lead to evolution and genetic disease. Further improvements in time resolution and noise reduction of single-molecule studies will uncover deeper mechanistic understanding of this critical, first step in evolution.

SUBMITTER: Pugliese KM

PROVIDER: S-EPMC5723536 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Recent progress in dissecting molecular recognition by DNA polymerases with non-native substrates.

Pugliese Kaitlin M KM Weiss Gregory A GA

Current opinion in chemical biology 20171102

DNA polymerases must discriminate the correct Watson-Crick base pair-forming deoxynucleoside triphosphate (dNTP) substrate from three other dNTPs and additional triphosphates found in the cell. The rarity of misincorporations in vivo, then, belies the high tolerance for dNTP analogs observed in vitro. Advances over the last 10 years in single-molecule fluorescence and electronic detection of dNTP analog incorporation enable exploration of the mechanism and limits to base discrimination by DNA po ...[more]

PMID: 29096323

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