诱导的异位子运动器组装绕过了对CENP-A核细胞组的要求
Karen E Gascoigne1, Kozo Takeuchi, Aussie Suzuki
1Whitehead Institute for Biomedical Research, Department of Biology, Nine Cambridge Center, MA 02142, USA.
Cell
|May 3, 2011
概括
两个关键蛋白质CENP-C和CENP-T对于构建基因,即确保细胞分裂期间精确分离染色体的细胞结构至关重要. 它们的DNA结合域直接指导动态组合,独立于CENP-A.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 精确的染色体分离对于细胞分裂至关重要,并依赖于在中心分子组装的动态基因复合体.
- 众所周知,中心基质子H3变体CENP-A可以指定中心基质子,但它不足以在人体细胞中完成动态基质子组装.
研究的目的:
- 调查构成性DNA结合性基因组件CENP-C和CENP-T在指导基因形成中的作用.
- 确定CENP-C和CENP-T是否可以独立于CENP-A驱动动力芯组件.
- 为了探索调节机制,如CENP-T酸化,在kinetochore组装.
主要方法:
- 改造了具有改变DNA结合区域的CENP-C和CENP-T蛋白质,以准异位染色体位置.
- 评估了动态芯组件的组装,包括KMN网络和Mad2.
- 评估了外阴动类焦点的微管附着和染色体分离.
- 研究了CENP-T酸化对动态组装的影响.
主要成果:
- 将CENP-C和CENP-T的DNA结合域替换为替代的向域,诱导了CENP-A独立的基因组在子宫外部位.
- 这些宫外运动器是功能性的,由构件的静态测量组合,微管附着物和Mad2招募证明.
- 含有焦点的染色体表现出适当的分离.
- 鉴定出CENP-T酸化是线粒分裂过程中内源性和异位性动脉组合的调节者.
结论:
- CENP-C 和 CENP-T 作为脊椎动物运动组装的关键平台.
- 这些蛋白质,通过它们的DNA结合能力,指导其他基因组件的招募,使功能性基因形成.
- CENP-T酸化提供了一种调节机制,用于控制动态组装动态.
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