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Structure of the origin recognition complex bound to DNA replication origin

机译：与DNA复制起点结合的起点识别复合物的结构

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摘要

The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 A cryo-electron microscopy structure of the Saccharomyces cerevisiae ORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.
机译：六亚基起源识别复合物（ORC）与DNA结合以标记真核生物中复制起始位点。在这里我们报告啤酒酵母ORC绑定到包含ARS共有序列（ACS）和B1元素的72个碱基对起源DNA序列的3 A低温电子显微镜结构。 ORC通过与磷酸盐骨架和碱基的广泛相互作用环绕DNA，并在ACS和B1位点弯曲DNA。 ACS中胸腺嘧啶残基的特异性识别是通过小沟中Orc1的保守碱性氨基酸基序，以及大沟中Orc4的物种特异性螺旋插入基序实现的。此外，分别通过Orc2和Orc5的基本补丁图案将类似的插入主要和次要凹槽的插入也嵌入B1位点，以接触碱基并弯曲DNA。这项工作指出了ORC在调节DNA结构以促进真核生物中来源选择和解旋酶上的保守作用。

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  • 来源
    《Nature》 |2018年第7713期|217-222|共6页
  • 作者

    Li Ningning; Lam Wai Hei; Zhai Yuanliang; Cheng Jiaxuan; Cheng Erchao; Zhao Yongqian; Gao Ning; Tye Bik-Kwoon;

  • 作者单位

    Peking Univ, State Key Lab Membrane Biol, Peking Tsinghua Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China;

    Tsinghua Univ, Sch Life Sci, Tsinghua Peking Ctr Life Sci, Beijing, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China;

    Peking Univ, State Key Lab Membrane Biol, Peking Tsinghua Ctr Life Sci, Sch Life Sci, Beijing, Peoples R China;

    Hong Kong Univ Sci & Technol, Div Life Sci, Hong Kong, Hong Kong, Peoples R China;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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