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- W2133644328 abstract "Microsatellite DNA synthesis represents a significant component of human genome replication that must occur faithfully. However, yeast replicative DNA polymerases do not possess high fidelity for microsatellite synthesis. We hypothesized that the structural features of Y-family polymerases that facilitate accurate translesion synthesis may promote accurate microsatellite synthesis. We compared human polymerases κ (Pol κ) and η (Pol η) fidelities to that of replicative human polymerase δ holoenzyme (Pol δ4), using the in vitro HSV-tk assay. Relative polymerase accuracy for insertion/deletion (indel) errors within 2-3 unit repeats internal to the HSV-tk gene concurred with the literature: Pol δ4 >> Pol κ or Pol η. In contrast, relative polymerase accuracy for unit-based indel errors within [GT](10) and [TC](11) microsatellites was: Pol κ ≥ Pol δ4 > Pol η. The magnitude of difference was greatest between Pols κ and δ4 with the [GT] template. Biochemically, Pol κ displayed less synthesis termination within the [GT] allele than did Pol δ4. In dual polymerase reactions, Pol κ competed with either a stalled or moving Pol δ4, thereby reducing termination. Our results challenge the ideology that pol κ is error prone, and suggest that DNA polymerases with complementary biochemical properties can function cooperatively at repetitive sequences." @default.
- W2133644328 created "2016-06-24" @default.
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- W2133644328 date "2011-10-22" @default.
- W2133644328 modified "2023-10-14" @default.
- W2133644328 title "Beyond translesion synthesis: polymerase κ fidelity as a potential determinant of microsatellite stability" @default.
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- W2133644328 doi "https://doi.org/10.1093/nar/gkr889" @default.
- W2133644328 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3287198" @default.
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