REGULATION OF DNA REPLICATION IN IRRADIATED CELLS

描述：(改编自申请人的摘要)：检查站保证 从一个细胞周期阶段到下一个细胞周期阶段的过程只有在 之前的活动已经完成。我们的长期目标是阐明 S期DNA损伤激活检查点的分子机制 导致DNA合成下调。需要解决的假设 通过这一建议，辐射诱导了一条信号转导途径 通过使复制中涉及的因子失活而使DNA复制停滞 入会仪式。目标是确定复制机制目标和 使用所获得的信息来定义信号转导途径。一个 将使用SV40体外复制系统。所有需要的组件都有 纯化的SV40大T抗原是唯一的非细胞 组件。具体目标包括：1)研究后翻译 RP-A的修饰和活性；2)翻译后研究 SV40T抗原的修饰和活性；3)研究 ATM、P53和P21对可导致RP-A和P21修饰的信号转导 SV40T抗原；4)开始提纯新的蛋白，涉及 发信号。

DESCRIPTION: (Adapted from the applicant's abstract): Checkpoints assure that progression from one cell cycle stage to the next proceeds only after previous events have been completed. The long-term goal is to elucidate the molecular mechanism of checkpoints activated by DNA damage in S phase, which results in down-regulation of DNA synthesis. The hypothesis to be addressed by this proposal is that radiation induces a signal transduction pathway that stalls DNA replication by inactivating factors involved in replication initiation. The goal is to identify the replication machinery targets and use the information gained to define the signal transduction pathway. An SV40 in vitro replication system will be used. All components needed have been purified and the SV40 large T antigen is the only non-cellular component. The specific aims include: 1) to study the post-translational modification and activity of RP-A; 2) to study the post-translational modification and activity of SV40 T antigen; 3) to study the contribution of ATM, p53 and p21 to signalling that can lead to modifications of RP-A and SV40 T antigen; and 4) to begin to purify novel proteins involved in signalling.