MECHANISM OF A DNA DAMAGE INDUCED CELL CYCLE CHECKPOINT

这个项目的目标是阐明DNA损伤如何阻止细胞 粟酒裂殖酵母有丝分裂前的一个周期， 人共济失调毛细血管扩张症基因的同源基因rad 3的作用 (ATM)，在这个过程中。在所有研究的胚胎后细胞中， 在G2期间的细胞周期阻滞导致细胞周期停滞在O2/M边界。这 检查点控制被认为需要AIM基因的产物或其 同源物，并通过抑制有丝分裂Cdk/细胞周期蛋白发挥功能 配合物In S.粟酒有10个基因已知是所需的DNA 损坏检查点，其中七个，包括rad 3，也需要 DNA合成检查点然而，DNA损伤和DNA合成 检查点通过不同的机制引起细胞周期停滞。DNA合成- 诱导的细胞周期停滞是由抑制性磷酸化引起的， Y15，而DNA损伤诱导细胞周期阻滞的机制是 独特的和无特征的。因此，目前有两个主要问题 关于S。粟酒酵母DNA损伤检查点。细胞周期如何 因DNA损伤在02/M边界被捕那么， 拉德基因的作用，这是需要的DNA损伤和DNA 合成检查点途径？

The goal of this project is to elucidate how DNA damage arrests the cell cycle before mitosis in Schizosaccharomyces pombe and to investigate the role of the gene rad3, a homolog of the human ataxia telangiectasia gene (ATM), in this process. In all studied post-embryonic cells, DNA damage during G2 leads to arrest of the cell cycle at the 02/M boundary. This checkpoint control is thought to require the product of AIM gene or its homologs and to function via the inhibition of the mitotic Cdk/cyclin complexes. In S. pombe there are ten genes known to be required for the DNA damage checkpoint, seven of which, including rad3, are also required for the DNA synthesis checkpoint. However, the DNA damage and DNA synthesis checkpoints cause cell cycle arrest by different mechanisms. DNA synthesis- induced cell cycle arrest is caused by the inhibitory phosphorylation on Y15 of Cdc2, while the mechanism of DNA damage-induced cell cycle arrest is distinct and uncharacterized. Thus, there are currently two major questions regarding the S. pombe DNA damage checkpoint. How is the cell cycle arrested at the 02/M boundary in response to DNA damage? And, what is the role of the rad genes that are required for both the DNA damage and DNA synthesis checkpoint pathways?