The RB69 DNA polymerase binding-pocket residue Tyr567 was shown previously to be a key determinant of fidelity because the replacement Y567A causes a powerful mutator activity. Ser565 is a nearby component of the binding pocket. Unlike Y567A, the replacement S565G has only a small impact on fidelity. However, combining Y567A and S565G reverses most of the mutator activity of Y567A. This is a unique and instructive observation in structural studies of polymerase fidelity, and we are working through a detailed examination of the mutational propensities of these constructs both in vivo and in vitro.
| Trzemecka, Anna; Jacewicz, Agata; Carver, Geraldine T et al. (2010) Reversal of a mutator activity by a nearby fidelity-neutral substitution in the RB69 DNA polymerase binding pocket. J Mol Biol 404:778-93 |
| Drake, John W (2009) Avoiding dangerous missense: thermophiles display especially low mutation rates. PLoS Genet 5:e1000520 |
