A Transition-State Perspective on Y-Family DNA Polymerase η Fidelity in Comparison with X-Family DNA Polymerases λ and β.

ABSTRACT: Deoxynucleotide misincorporation efficiencies can span a wide 10⁴-fold range, from ∼10^-2 to ∼10^-6, depending principally on polymerase (pol) identity and DNA sequence context. We have addressed DNA pol fidelity mechanisms from a transition-state (TS) perspective using our "tool-kit" of dATP- and dGTP-β,γ substrate analogues in which the pyrophosphate leaving group (p K_a4 = 8.9) has been replaced by a series of bisphosphonates covering a broad acidity range spanning p K_a4 values from 7.8 (CF₂) to 12.3 [C(CH₃)₂]. Here, we have used a linear free energy relationship (LFER) analysis, in the form of a Brønsted plot of log( k_pol) versus p K_a4, for Y-family error-prone pol η and X-family

SUBMITTER: Oertell K 

PROVIDER: S-EPMC6681824 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature