REGULATION OF DNA REPLICATION IN IRRADIATED CELLS

描述：（改编自申请人摘要）：检查点确保 从一个细胞周期阶段到下一个阶段的进程只有在 以前的活动已经完成。 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。 要解决的假设 辐射诱导了一条信号转导途径， 通过使复制因子失活来阻止DNA复制 入会仪式 目标是确定复制机制的目标， 使用获得的信息来定义信号转导途径。 一个 将使用SV 40体外复制系统。 所需的所有组件都具有 SV 40大T抗原是唯一的非细胞抗原， 成分 具体目的包括：1）研究翻译后 RP-A的修饰和活性; 2）研究RP-A的翻译后修饰， 研究SV 40 T抗原的修饰和活性， ATM、p53和p21与可导致RP-A修饰的信号传导有关， SV 40 T抗原;和4）开始纯化涉及 信号装置.

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.