核ARP2/3驱动DNA断裂聚类以进行同质导向的修复
Benjamin R Schrank1, Tomas Aparicio1, Yinyin Li2
1Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Nature
|June 22, 2018
概括
核活性蛋白和ARP2/3复合体在同质导向修复 (HDR) 过程中驱动DNA双链断裂的运动. 这种基于actin的移动性对于G2阶段细胞中高效HDR所必需的修复域的形成至关重要.
科学领域:
- 细胞生物学
- 分子生物学
- 遗传学
背景情况:
- 通过非同源端连接 (NHEJ) 或同源导向修复 (HDR) 来修复DNA双链断裂 (DSB).
- 虽然NHEJ涉及有限的DNA末端处理和染色体移动性,但HDR表现出广泛的处理和增强的运动.
- 与HDR相关的DNA运动背后的分子机制在很大程度上是未知的.
研究的目的:
- 在DNA双链断裂的同质导向修复过程中研究染色质流动性的分子基础.
- 确定核活性蛋白和相关蛋白质在DNA修复途径中的作用.
主要方法:
- 使用了Xenopus laevis无细胞提取物和哺乳动物细胞模型.
- 研究了核动蛋白,WASP和ARP2/3复合物的受损染色体的招募.
- 评估了抑制actin核化对DNA终端处理和修复的影响.
主要成果:
- 核动因,WASP和ARP2/3复合物被招募到经过HDR的DSB中.
- 核活性聚合驱动DSBs的一个子集迁移到亚核集群.
- 在G2细胞周期阶段,主动蛋白驱动的移动性特别影响HDR.
- 抑制动蛋白核化会影响DNA末端处理和HDR.
- ARP2/3复合体没有参与NHEJ.
结论:
- 基于核激素的移动性通过创建HDR必不可少的修复域来塑造染色体组织.
- 乙聚合是同质导向修复的关键调节器,与非同质端结合不同.
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