...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Phosphorylation of FANCD2 on Two Novel Sites Is Required for Mitomycin C Resistance
【24h】

Phosphorylation of FANCD2 on Two Novel Sites Is Required for Mitomycin C Resistance

机译：丝裂霉素C耐药性需要两个新位点上的FANCD2磷酸化。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The Fanconi anemia (FA) pathway is a DNA damage-activated signaling pathway which regulates cellular resistance to DNA cross-linking agents. Cloned FA genes and proteins cooperate in this pathway, and monoubiquitination of FANCD2 is a critical downstream event. The cell cycle checkpoint kinase ATR is required for the efficient monoubiquitination of FANCD2, while another checkpoint kinase, ATM, directly phosphorylates FANCD2 and controls the ionizing radiation (IR)-inducible intra-S-phase checkpoint. In the present study, we identify two novel DNA damage-inducible phosphorylation sites on FANCD2, threonine 691 and serine 717. ATR phosphorylates FANCD2 on these two sites, thereby promoting FANCD2 monoubiquitination and enhancing cellular resistance to DNA cross-linking agents. Phosphorylation of the sites is required for establishment of the intra-S-phase checkpoint response. IR-inducible phosphorylation of threonine 691 and serine 717 is also dependent on ATM and is more strongly impaired when both ATM and ATR are knocked down. Threonine 691 is phosphorylated during normal S-phase progression in an ATM-dependent manner. These findings further support the functional connection of ATM/ATR kinases and FANCD2 in the DNA damage response and support a role for the FA pathway in the coordination of the S phase of the cell cycle.
机译：范可尼贫血（FA）途径是DNA损伤激活的信号传导途径，可调节细胞对DNA交联剂的抗性。克隆的FA基因和蛋白质在该途径中协同作用，FANCD2的单泛素化是关键的下游事件。细胞周期检查点激酶ATR是FANCD2高效单泛素化所必需的，而另一个检查点激酶ATM直接使FANCD2磷酸化并控制电离辐射（IR）诱导的S期内检查点。在本研究中，我们在FANCD2上识别了两个新的可诱导DNA损伤的磷酸化位点，苏氨酸691和丝氨酸717。ATR使这两个位点上的FANCD2磷酸化，从而促进FANCD2单泛素化并增强了细胞对DNA交联剂的抵抗力。建立S阶段内检查点响应需要位点的磷酸化。苏氨酸691和丝氨酸717的IR诱导磷酸化也取决于ATM，并且当ATM和ATR都被击倒时，磷酸化的程度会大大降低。苏氨酸691在正常S期进程中以ATM依赖性方式被磷酸化。这些发现进一步支持了ATM / ATR激酶和FANCD2在DNA损伤反应中的功能连接，并支持了FA途径在细胞周期S期协调中的作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号