Rutberg S E, Dolan L R, Ronai Z
Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY 10595.
DNA Cell Biol. 1994 Aug;13(8):865-74. doi: 10.1089/dna.1994.13.865.
Previously, we have shown that integrated copies of polyoma DNA can be induced to replicate in rat fibroblasts (H3 cells) exposed to a DNA-damaging agent. In the current study, we demonstrate that UV-irradiation of mouse fibroblasts (WOP cells), transiently transfected with polyoma DNA, results in repression of polyoma replication. Cotransfection of oligomers representing wild-type but not mutated forms of the PEBP2 target sequence restored levels of viral replication indicating a role of PEBP2 binding proteins in mediating this effect. DNA-binding assays revealed that a different subset of complexes was formed with the PEBP2 target sequence when nuclear proteins from sham and UV-irradiated WOP and H3 cells were compared, suggesting that the activities of PEBP2 binding proteins are differentially regulated upon UV-irradiation in these two cell types. The ability of PEBP2 to modulate polyoma replication following UV-irradiation in WOP cells suggests a potential role of PEBP2 proteins in the cellular response to DNA damage.
此前，我们已经表明，多瘤病毒DNA的整合拷贝在暴露于DNA损伤剂的大鼠成纤维细胞（H3细胞）中可被诱导复制。在当前研究中，我们证明，对瞬时转染了多瘤病毒DNA的小鼠成纤维细胞（WOP细胞）进行紫外线照射，会导致多瘤病毒复制受到抑制。共转染代表野生型而非突变形式的PEBP2靶序列的寡聚物可恢复病毒复制水平，这表明PEBP2结合蛋白在介导这一效应中发挥作用。DNA结合试验表明，当比较假处理组以及紫外线照射后的WOP和H3细胞的核蛋白与PEBP2靶序列形成的复合物时，会形成不同的复合物亚群，这表明在这两种细胞类型中，紫外线照射后PEBP2结合蛋白的活性受到不同调节。在WOP细胞中，紫外线照射后PEBP2调节多瘤病毒复制的能力表明，PEBP2蛋白在细胞对DNA损伤的反应中可能发挥作用。
