S459F : Biochemical assays

The S459F substitution in human POLE and the analogous S474F substitution in Saccharomyces cerevisiae Pol2 severely reduce the exonuclease activity and increase the polymerase error rate in vitro. Data in yeast also indicate increased DNA polymerase activity.

• Shinbrot, E. et al. Exonuclease mutations in DNA polymerase epsilon reveal replication strand specific mutation patterns and human origins of replication. Genome Res 24, 1740-50 (2014). pubmed.ncbi.nlm.nih.gov/25228659/
• Barbari, S.R. et al. Enhanced polymerase activity permits efficient synthesis by cancer-associated DNA polymerase ε variants at low dNTP levels. Nucleic Acids Res 50, 8023-8040 (2022). https://pubmed.ncbi.nlm.nih.gov/35822874/