STUDIES OF DNA POLYMERASES

我们的长期目标有两个：了解哪些因素维持或 扰乱哺乳动物DNA聚合酶的保真度并了解 这些酶和相关的DNA酶一起参与DNA切除修复。 在不久的将来，我们建议研究DNA中发生的变化 由于种群原因，细胞进入非循环状态时的聚合酶α G-O因中度疲劳而衰老、分化或停滞。我们 我还建议研究这些变化以及如何通过 蛋白激酶C影响DNA聚合酶的保真度和活性水平 阿尔法。最后，几种复杂形式的DNA聚合酶α、β和 将对Delta进行研究以了解影响 富达。 使用非常明确的受损DNA和染色质底物，我们还建议 研究几种形式的阿尔法介导的切除和修复合成， β和Delta聚合酶和Gamma聚合酶，每一个单独和在 与发现与这些酶相关的DNA酶结合。 最后，我们将220千道尔顿因子提纯为齐次因子 在通透性细胞中DNA修复合成所需的，我们建议 研究该因子的催化特性及其可能的关系 DNA聚合酶Delta。

Our long term goals are two-fold: to understand what factors maintain or perturb the fidelity of mammalian DNA polymerases and to understand how these enzymes along with associated DNases take part in DNA excision repair. In the immediate future we propose to study changes which occur in DNA polymerase Alpha as the cell enters a non-cycling state due to population senescence, differentiation or arrest in G-o due to medium exhaustion. We also propose to study how these changes as well as phosphorylation by protein kinase C affect the fidelity and activity levels of DNA polymerase Alpha. Finally, several complex forms of DNA polymerases Alpha, Beta and Delta would be studied in order to learn about factors which affect fidelity. Using very defined damaged DNA and chromatin substrates we propose also to study excision and repair synthesis mediated by several forms of Alpha, Beta and Delta polymerase and by Gamma polymerase, each alone and in conjunction with DNases found to be associated with these enzymes. Finally, we have purified to homogeneity a 220 kilodalton factor which is required for DNA repair synthesis in permeabilized cells and we propose to study the catalytic properties of this factor and its possible relation to DNA polymerase Delta.