MECHANISMS OF CELL PROLIFERATION FOLLOWING PERTURBATIONS

拟议研究的目的是确定 在G1-过境后的可逆加速机制 阻断细胞周期在S期的进展， 一代 这种现象的一个可能机制是， S期的延迟进展可以触发生化过程 在完成之前的后续G1阶段， 分裂。 在具体目标1中，我们将确定细胞周期 在HeLa细胞中导致G1加速的扰动具有类似的 在正常和转化的其他人类细胞系中的作用 表型 详细的动力学分析将用于完全 映射能力窗口，即，细胞周期时间从早期 S期和M期，延迟进展导致G1- 加速度 在具体目标2中，将确定加速G 1是否 转运是由于已知的G1- 调节蛋白 具体目标3中提出的工作将 确定S相后的加速G1-转变是否 扰动导致非计划性的失活， 并确定视网膜母细胞瘤蛋白，是否有这样的机制 能消除电离辐射引起的G1期阻滞。 在特定 目的4我们将确定哪些特定的mRNA种类有助于 在Aim 2中观察到G1调节蛋白表达的改变 与G1加速度有关 获得的结果 从完成这项研究将表征机制 参与从细胞周期扰动中恢复，并验证了这一想法 早期G1期事件会受到生化过程的影响， 在有丝分裂完成之前发生的。

The objective of the proposed research is to determine the mechanisms of acceleration in G 1- transit following a reversible block of cell cycle progression in S-phase of the preceding generation. A possible mechanism for this phenomenon is that delayed progression in S-phase can trigger biochemical processes pertinent to the subsequent G 1-phase prior to the completion of mitosis. In Specific Aim 1, we will determine if cell cycle perturbations that lead to G 1- acceleration in HeLa cells have similar effects in other human cell lines of both normal and transformed phenotypes. Detailed kinetic analyses will be used to completely map the competence window, i.e., the cell cycle time between early S and M phases in which delayed progression results in G 1- acceleration. In Specific Aim 2, will determine if accelerated G 1 transit is due to an alteration in the expression of known G 1- regulatory proteins. The work proposed in Specific Aim 3 will determine whether accelerated G 1-transit following S-phase perturbation results in an unscheduled inactivation of the Retinoblastoma protein and determine, whether such a mechanism can abrogate the ionizing radiation-induced G 1-arrest. In Specific Aim 4 we will determine which specific mRNA species contribute to the altered expression of G 1-regulatory proteins observed in Aim 2 which are associated with G 1-acceleration. The results obtained from completion of this study will characterize the mechanisms involved in recover from cell-cycle perturbation, and verify the idea that early G1 events can be influenced by biochemical processes occurring prior to the completion of mitosis.