Functional Analysis of Cancer-Associated DNA Polymerase ε Variants in Saccharomyces cerevisiae.

ABSTRACT: DNA replication fidelity relies on base selectivity of the replicative DNA polymerases, exonucleolytic proofreading, and postreplicative DNA mismatch repair (MMR). Ultramutated human cancers without MMR defects carry alterations in the exonuclease domain of DNA polymerase ε (Polε). They have been hypothesized to result from defective proofreading. However, modeling of the most common variant, Polε-P286R, in yeast produced an unexpectedly strong mutator effect that exceeded the effect of proofreading deficiency by two orders of magnitude and indicated the involvement of other infidelity factors. The in vivo consequences of many additional Polε mutations reported in cancers remain poorly understood. Here, we genetically characterized 13 cancer-associated Polε variants in the yeast sys

SUBMITTER: Barbari SR 

PROVIDER: S-EPMC5844290 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature