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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >A single-molecule characterization of p53 search on DNA
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A single-molecule characterization of p53 search on DNA

机译：DNA上p53搜索的单分子表征

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摘要

The tumor suppressor p53 slides along DNA while searching for its cognate site. Central to this process is the basic C-terminal domain, whose regulatory role and its coordination with the core DNA-binding domain is highly debated. Here we use single-molecule techniques to characterize the search process and disentangle the roles played by these two DNA-binding domains in the search process. We demonstrate that the C-terminal domain is capable of rapid translocation, while the core domain is unable to slide and instead hops along DNA. These findings are integrated into a model, in which the C-terminal domain mediates fast sliding of p53, while the core domain samples DNA by frequent dissociation and reassociation, allowing for rapid scanning of long DNA regions. The model further proposes how modifications of the C-terminal domain can activate "latent" p53 and reconciles seemingly contradictory data on the action of different domains and their coordination.
机译：肿瘤抑制因子p53沿着DNA滑动，同时寻找其同源位点。这个过程的核心是基本的C末端结构域，其调节作用及其与核心DNA结合结构域的协调受到了激烈的争论。在这里，我们使用单分子技术来表征搜索过程，并解开这两个DNA结合域在搜索过程中的作用。我们证明，C末端域能够快速易位，而核心域却无法滑动，而是沿着DNA跳跃。这些发现被整合到一个模型中，其中C末端结构域介导p53的快速滑动，而核心结构域通过频繁的解离和重新结合对DNA采样，从而可以快速扫描长的DNA区域。该模型还提出了C末端结构域的修饰如何激活“潜在” p53并调和关于不同结构域的作用及其协调的看似矛盾的数据。

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    Anahita Tafvizi; Fang Huang; Alan R. Fersht; Leonid A. Mirny; Antoine M. van Oijen;

  • 作者单位

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Seeley G. Mudd 204A, Boston, MA 02115,Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, 77 Massachusetts Avenue, E25-526C Cambridge, MA 02139;

    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 OQH, Uhited Kingdom;

    Medical Research Council Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 OQH, Uhited Kingdom;

    Harvard-Massachusetts Institute of Technology Division of Health Sciences and Technology, 77 Massachusetts Avenue, E25-526C Cambridge, MA 02139;

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 250 Longwood Avenue, Seeley G. Mudd 204A, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    recognition; response element; transcription factor;

    机译：承认;响应元素转录因子;

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