Investigation of the restart mechanisms of stalled DNA replication forks.

精确的DNA复制对所有生物体都很重要。如果DNA复制不能正常完成，这些生物体就不能维持细胞代谢。由于DNA损伤导致DNA复制不完全而导致DNA复制停滞，所有生物体都提供对停滞的DNA复制分叉的修复。在这里，我们致力于了解哺乳动物细胞中DNA复制叉的停滞机制。我们之前的研究表明，mus81结构特异性内切酶参与了停滞复制分叉的修复。因此，我们首先研究了MUS81在DNA损伤网络中的调控机制。预期，atr相关的损伤反应首先发生。然后引入mus81依赖性DNA断裂。在此之后，发生了依赖于atm的响应。这个网络对于鼓励修理失速的叉子是很重要的。此外，我们还对一些与mus81无关的通路进行了筛选，发现了一些候选通路。我们现在正在描述这些候选因子的生化功能。

Precise DNA replication is important for all organism. If DNA replication does not complete properly, these organisms cannot maintain their cellular metabolisms. Since DNA replication stalls by DNA damages causes of incomplete DNA replication, all oraganisms provide the repair of stalled DNA replication forks. Here we addressed to understand the mechanisms of stalled DNA replication forks in mammalian cells. We previously showed that the MUS81-structure specific endonuclease is involved in the repair of stalled replication forks. Therefore, we first investigated how MUS81 is regulated in DNA damage networks. Expectedly, ATR-dependent damage responses occur at first. Then MUS81-dependent DNA breakages were introduced. Following this, ATM-dependent responses occurred. This network is important to encourage the repair of stalled forks. In addition, we have done the screening of MUS81-independent pathways and found several candidates. We are now characterizing the biochemical functions of these candidate factors.