一个DNA损伤反应屏幕识别了RHINO,这是ATR信号传递所需的9-1-1和TopBP1相互作用蛋白质
Cecilia Cotta-Ramusino1, E Robert McDonald, Kristen Hurov
1Department of Genetics, Harvard University Medical School, Howard Hughes Medical Institute, Division of Genetics, Brigham and Women's Hospital, Boston, MA 02115, USA.
Science (New York, N.Y.)
|June 11, 2011
概括
研究人员确定了RHINO,这是一种对DNA损伤反应 (DDR) 至关重要的蛋白质. 犀牛与其他蛋白质合作,激活ATR信号,这对于DNA修复和细胞循环停止至关重要.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 遗传学 是一个遗传学.
背景情况:
- DNA损伤反应 (DDR) 是一个复杂的细胞通路网络,可以检测和修复DNA损伤.
- 细胞循环停止是DDR的关键结果,防止受损细胞复制.
研究的目的:
- 为了确定参与DDR途径的新型蛋白质.
- 阐明非特征蛋白在ATR信号传递和细胞循环停止中的作用.
主要方法:
- 查缺乏DNA损伤引起的细胞循环停止的细胞.
- 使用分子生物学技术,研究DNA损伤部位的蛋白质相互作用.
主要成果:
- 一个屏幕识别了缺乏损伤诱导的细胞循环停止的细胞,揭示了Fanconi贫血和同源重组蛋白在ATR信号传递中的作用.
- 三个候选DDR蛋白,INTS7,CLOCK和RHINO,被招募到DNA损伤部位.
- 发现RHINO独立地与Rad9-Rad1-Hus1 (9-1-1) 复合体和TopBP1.1结合.
- 9-1-1综合体对DNA损伤部位的RHINO的招募促进了Chk1的激活.
结论:
- 犀牛在ATR信号传输中发挥着至关重要的作用,它通过桥接9-1-1综合体和TopBP1.
- 犀牛,9-1-1复合体和TopBP1一起起作用,完全激活DDR中的关键激酶ATR.
- 这些发现揭示了ATR激活的新型机制,并突出了RHINO作为DNA修复途径的潜在治疗点.
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