Komatsu K, Wharton W, Hang H, Wu C, Singh S, Lieberman H B, Pledger W J, Wang H G
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida, FL 33612, USA.
Oncogene. 2000 Nov 2;19(46):5291-7. doi: 10.1038/sj.onc.1203901.
The hHus1 and several hRad proteins are involved in the control of DNA integrity checkpoints, although the mechanisms underlying these processes are unknown. Using a yeast two-hybrid system to detect protein-protein interactions, we found that human proliferating cell nuclear antigen (PCNA), a protein known to function in both DNA replication and repair, interacts with the human checkpoint-related protein Hus1 (hHus1). In human skin fibroblast cells, exposure to ionizing radiation of hydroxyurea triggers translocation of hHus1 from the cytosol to the nucleus, where it associates with PCNA as well as another checkpoint protein, hRad9. This nuclear translocation and the complex formation or hHus1 with PCNA and hRad9 correlate closely with changes in cell cycle distribution in response to radiation exposure. These results suggest that this multi-protein complex may be important for coordinating cell-cycle progression, DNA replication and repair of damaged DNA.
人Hus1和几种人Rad蛋白参与DNA完整性检查点的调控，尽管这些过程背后的机制尚不清楚。利用酵母双杂交系统检测蛋白质-蛋白质相互作用，我们发现人增殖细胞核抗原（PCNA），一种已知在DNA复制和修复中起作用的蛋白质，与人检查点相关蛋白Hus1（hHus1）相互作用。在人皮肤成纤维细胞中，暴露于羟基脲的电离辐射会触发hHus1从细胞质转移到细胞核，在细胞核中它与PCNA以及另一种检查点蛋白hRad9结合。这种核转位以及hHus1与PCNA和hRad9的复合物形成与辐射暴露后细胞周期分布的变化密切相关。这些结果表明，这种多蛋白复合物可能对协调细胞周期进程、DNA复制和受损DNA的修复很重要。
