He Z, Brinton B T, Greenblatt J, Hassell J A, Ingles C J
Department of Molecular and Medical Genetics, University of Toronto, Canada.
Cell. 1993 Jun 18;73(6):1223-32. doi: 10.1016/0092-8674(93)90650-f.
Many transcription factors can activate the initiation of DNA replication. We have used affinity chromatography to show that the acidic activation domains of the transcription factors VP16, GAL4, and p53 each bind selectively to human and yeast replication factor A (RPA). The binding is direct and to the largest subunit of the trimeric RPA complex, RPA-1. Mutations in VP16 that reduce the ability of GAL4-VP16 to activate polyomavirus DNA replication also compromise the binding of VP16 to RPA. We suggest that transcription factors may interact with RPA either to stabilize single-stranded DNA at a replication origin or to recruit DNA polymerase alpha to the replication initiation complex.
许多转录因子可激活DNA复制的起始过程。我们利用亲和层析法证明，转录因子VP16、GAL4和p53的酸性激活结构域均能选择性地与人及酵母复制因子A（RPA）结合。这种结合是直接的，且针对三聚体RPA复合物的最大亚基RPA-1。降低GAL4-VP16激活多瘤病毒DNA复制能力的VP16突变，也会损害VP16与RPA的结合。我们认为，转录因子可能与RPA相互作用，要么在复制起点稳定单链DNA，要么将DNA聚合酶α招募至复制起始复合物。
