Kinetic mechanism of DNA polymerases: contributions of conformational dynamics and a third divalent metal ion
Faithful transmission and maintenance of genetic material is primarily fulfilled by DNA
polymerases. During DNA replication, these enzymes catalyze incorporation of …
polymerases. During DNA replication, these enzymes catalyze incorporation of …
Structural basis of HIV inhibition by L-nucleosides: Opportunities for drug development and repurposing
FX Ruiz, A Hoang, CR Dilmore, JJ DeStefano… - Drug discovery today, 2022 - Elsevier
Highlights•L-NRTI-TP drugs bind RT/nucleic acid in a non-productive conformation for
chemistry.•Binding affinity is similar to D stereoisomers but incorporation rate is very slow.•L …
chemistry.•Binding affinity is similar to D stereoisomers but incorporation rate is very slow.•L …
Structural basis for processive daughter-strand synthesis and proofreading by the human leading-strand DNA polymerase Pol ε
JJ Roske, JTP Yeeles - Nature Structural & Molecular Biology, 2024 - nature.com
During chromosome replication, the nascent leading strand is synthesized by DNA
polymerase epsilon (Pol ε), which associates with the sliding clamp processivity factor …
polymerase epsilon (Pol ε), which associates with the sliding clamp processivity factor …
Elucidating molecular interactions of L-nucleotides with HIV-1 reverse transcriptase and mechanism of M184V-caused drug resistance
M Hung, EJ Tokarsky, L Lagpacan, L Zhang… - Communications …, 2019 - nature.com
Abstract Emtricitabine (FTC) and lamivudine (3TC), containing an oxathiolane ring with
unnatural (−)-stereochemistry, are widely used nucleoside reverse transcriptase inhibitors …
unnatural (−)-stereochemistry, are widely used nucleoside reverse transcriptase inhibitors …
A polar filter in DNA polymerases prevents ribonucleotide incorporation
The presence of ribonucleotides in DNA can lead to genomic instability and cellular lethality.
To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) …
To prevent adventitious rNTP incorporation, the majority of the DNA polymerases (dPols) …
Significant impact of divalent metal ions on the fidelity, sugar selectivity, and drug incorporation efficiency of human PrimPol
EJ Tokarsky, PC Wallenmeyer, KK Phi, Z Suo - DNA repair, 2017 - Elsevier
Human PrimPol is a recently discovered bifunctional enzyme that displays DNA template-
directed primase and polymerase activities. PrimPol has been implicated in nuclear and …
directed primase and polymerase activities. PrimPol has been implicated in nuclear and …
Ribonucleotides in bacterial DNA
JW Schroeder, JR Randall, LA Matthews… - Critical reviews in …, 2015 - Taylor & Francis
In all living cells, DNA is the storage medium for genetic information. Being quite stable,
DNA is well-suited for its role in storage and propagation of information, but RNA is also …
DNA is well-suited for its role in storage and propagation of information, but RNA is also …
Mechanistic basis for the bypass of a bulky DNA adduct catalyzed by a Y-family DNA polymerase
R Vyas, G Efthimiopoulos, EJ Tokarsky… - Journal of the …, 2015 - ACS Publications
1-Nitropyrene (1-NP), an environmental pollutant, induces DNA damage in vivo and is
considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall …
considered to be carcinogenic. The DNA adducts formed by the 1-NP metabolites stall …
Mirror-image thymidine discriminates against incorporation of deoxyribonucleotide triphosphate into DNA and repairs itself by DNA polymerases
Y Xiao, Q Liu, X Tang, Z Yang, L Wu… - Bioconjugate Chemistry, 2017 - ACS Publications
DNA polymerases are known to recognize preferably d-nucleotides over l-nucleotides
during DNA synthesis. Here, we report that several general DNA polymerases catalyze …
during DNA synthesis. Here, we report that several general DNA polymerases catalyze …
Replicative bypass studies of l-deoxyribonucleosides in Vitro and in E. coli cell
Y Kan, Z Jin, Y Ke, D Lin, L Yan, L Wu, Y He - Scientific Reports, 2022 - nature.com
Abstract l-nucleosides were the most important antiviral lead compounds because they can
inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead to …
inhibit viral DNA polymerase and DNA synthesis of many viruses, whereas they may lead to …