Structure-Function Studies Of DNA Replication Fidelity

今年，我们发布了以下成果。(1)我们鉴定了酵母DNA聚合酶Zeta的一个突变子衍生物，它在确定真核生物的自发诱变率和DNA损伤诱变率方面具有关键作用。(2)与LSB计算小组合作，研究了人DNA聚合酶lambda的催化机理。(3)在填补缺口的DNA修复合成过程中，DNA聚合酶lambda将尚未复制的模板碱基压缩在由三个保守氨基酸组成的结合口袋中。(4)我们研究了DNA聚合酶Delta和ETA在8-氧鸟嘌呤跨损伤DNA合成中的作用，8-氧鸟嘌呤是氧化应激引起的最常见和最具突变性的损伤之一。(5)综述了主要的复制型DNA聚合酶在先导链和滞后链DNA合成中的作用，以及实现高保真DNA复制的机制。此外，我们在DNA复制和聚合酶功能的其他几个方面取得了实质性的进展，但尚未发表。

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 In addition, we made substantial, but as yet unpublished, progress on the several other aspects of DNA replication and polymerase functions.