Structure-Function Studies Of DNA Replication Fidelity

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This year, we published the following accomplishments. (1) We characterized a mutator derivative of yeast DNA polymerase zeta, which has a critical role in determining the rate of both spontaneous and DNA damage-induced mutagenesis in eukaryotes. (2) In collaboration with the computational group in LSB, we investigated the mechanism of catalysis by human DNA polymerase lambda. (3) We demonstrated that during gap filling DNA repair synthesis, DNA polymerase lambda scrunches the yet-to-be-copied template base in a binding pocket comprised of three conserved amino acids. (4) We investigated the roles of DNA polymerases delta and eta in translesion DNA synthesis of 8-oxo-guanine, one of the most common and mutagenic lesions resulting from oxidative stress. (5) We published comprehensive reviews on the roles of the major replicative DNA polymerases in leading strand and lagging strand DNA synthesis, and on mechanisms by which high fidelity DNA replication is achieved. In addition, we made substantial, but as yet unpublished, progress on the several other aspects of DNA replication and polymerase functions.