Investigating of a Novel Checkpoint in S. Cerevisiae

描述（由申请人提供）： 先前的工作已经表明，来源缺陷的YAC（5ORIdeltaYAC）诱导新的检查点。这个检查点不依赖于DNA损伤。它也不同于HU诱导的复制检查点，因为复制叉不会停止，Rad53也不会被激活。因此，假设这种新的检查点监测正在进行的DNA合成。 有趣的是，发现Rad9对于维持该检查点至关重要，表明Rad9在正常细胞周期中监测S期进展中的先前未知作用。将进行遗传筛选，以确定这种新的检查点途径的其他组成部分。这项工作将有助于我们了解检查点机制如何在未受干扰的细胞周期中运作。它还将进一步了解癌细胞如何逃脱细胞周期和检查点控制，导致基因组不稳定。

DESCRIPTION (provided by applicant): Previous work has shown that an origin-deficient YAC (5ORIdeltaYAC) induces a novel checkpoint. This checkpoint is independent of DNA damage. It is also different from the HU-induced replication checkpoint because replication forks do not stall and Rad53 is not activated. Therefore, it was postulated that this novel checkpoint monitors ongoing DNA synthesis. Interestingly, Rad9 was found essential for maintaining this checkpoint, indicating a previously unknown role of Rad9 in monitoring S phase progression in a normal cell cycle. A genetic screen will be conducted to identify additional components of this novel checkpoint pathway. This work will contribute to our understanding of how checkpoint mechanisms operate during an unperturbed cell cycle. It will also further our understanding of how cancer cells escape cell cycle and checkpoint control, leading to genome instability.