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。 裂殖酵母有丝分裂前周期的研究 人类共济失调毛细血管扩张症基因的同源基因Rad3的作用 (ATM)，在这个过程中。在所有研究的胚胎后细胞中，DNA损伤 G2期导致细胞周期停滞于02/M交界处。这 检查点控制被认为需要AIM基因的产物或其 同系物并通过抑制有丝分裂CDK/Cyclin发挥作用 复合体。在S.pombe中，有10个已知的基因是DNA所必需的 损坏检查站，其中包括RAD3在内的7个检查站也需要 DNA合成检查站。然而，DNA损伤和DNA合成 检查点通过不同的机制导致细胞周期停滞。DNA合成- 诱导的细胞周期停滞是由抑制磷酸化引起的 Y15，而DNA损伤诱导细胞周期停滞的机制是 独特的，没有特征的。因此，目前存在两个主要问题 关于S.pombe DNA损伤检查站。细胞周期如何？ 因DNA损伤而在02/M边界被捕？那么，什么是 DNA损伤和DNA损伤所需的rad基因的作用 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?