Investigation of the restart mechanisms of stalled DNA replication forks.

研究停滞的 DNA 复制叉的重启机制。

• 批准号: 23770208
• 负责人: HANADA Katsuhiro
• 金额: $ 2.91万
• 依托单位: Oita University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23770208/
• 关键词: DNA損傷・修復

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.

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它们的细胞代谢。由于DNA复制停滞是由DNA损伤导致的DNA复制不完整，所有的有机体都提供了停滞的DNA复制叉的修复。在这里，我们致力于了解哺乳动物细胞中停滞的DNA复制叉的机制。我们以前表明，MUS81结构特异性核酸内切酶参与修复停滞的复制叉。因此，我们首先研究了MUS81在DNA损伤网络中的调节方式。预期的是，ATR依赖的损伤反应首先发生。然后引入依赖于MUS81的DNA断裂。在此之后，发生了ATM依赖性反应。这个网络对于鼓励修复停滞的分叉很重要。此外，我们还对MUS81非依赖性通路进行了筛选，发现了几条候选通路。我们现在正在描述这些候选因子的生化功能。

项目成果

ピロリ菌感染後の染色体不安定性に関する発表

幽门螺杆菌感染后染色体不稳定的介绍

• 发表时间: 2011
• 作者: Katsuhiro Hanada;Yoshio Yamaoka
• 通讯作者: Yoshio Yamaoka