Loading mechanism of DNA polymerases to replication origin

DNA聚合酶复制起点的加载机制

基本信息

  • 批准号:
    11694331
  • 负责人:
  • 金额:
    $ 5.25万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (A).
  • 财政年份:
    1999
  • 资助国家:
    日本
  • 起止时间:
    1999 至 2000
  • 项目状态:
    已结题

项目摘要

Dpb11 of budding yeast has four BRCT (BRCA1 C-Terminus) repeats, which function for protein-protein interactions, and it is required for DNA replication and cell cycle checkpoint. We also isolated Sld(synthetic lethality with dpb11-1)1〜6. In this study, we revealed those described below.1) Dpb11 forms a complex with DNA polymerase ε and is required for loading of DNA polymerase to replication origins. 2) When DNA replication is inhibited by hydroxyl urea, associations of DNA replication enzymes with late-firing origins are blocked. In dpb11-1 cells, this block is released, like other checkpoint mutants. Thus, it seems likely that Dpb11 functions for the checkpoint through the block of late-firing origins. 3) Sld3, like Cdc45, associates with early-firing origins in G1 phase and with late-firing origins in S phase. 4) Sld3 and Cdc45 form a complex and this complex formation is required for origin associations of both proteins. 5) The origin associations of Sld3 and Cdc45 is required for the origin unwinding. 6) Sld5 and Psf1 (Partner of sld five) form a complex which associates with replication origins in S phase and is required for origin association of DNA polymerase.7) Sld2 which form a complex with Dpb11 is phosphorylated in S phase and this phosphorylation depends on S-Cdk activity. Only the phosphorylated form of Sld2 form a complex with Dpb11, which is required for further loading of DNA polymerase. Thus, S-Cdk controls the initiation of DNA replication through phosphorylation of Sld2. Taken all together, Dpb11 together with Sld proteins functions for loading of DNA polymerase to replication origins. Future analysis will give a clear view for origin lading of DNA polymerase.
芽殖酵母的Dpb11具有4个BRCT (BRCA1 C-Terminus)重复序列,其功能是蛋白质相互作用,是DNA复制和细胞周期检查点所必需的。我们还分离到dpb11-1的合成致死性Sld(synthetic lethality)1 ~ 6。在这项研究中,我们揭示了以下描述。1) Dpb11与DNA聚合酶ε形成复合体,是将DNA聚合酶装载到复制起点所必需的。2)当DNA复制被羟基脲抑制时,DNA复制酶与迟发起源的关联被阻断。在dpb11-1细胞中,像其他检查点突变体一样,该块被释放。因此,Dpb11似乎很可能通过阻滞迟发起源来为检查点起作用。3) Sld3与Cdc45一样,与G1期的早发起源和S期的晚发起源有关。4) Sld3和Cdc45形成一个复合体,这个复合体的形成是两种蛋白起源结合所必需的。5)起始点解绕需要Sld3和Cdc45的起始点关联。6) Sld5和Psf1 (Sld5的伴侣)在S期形成与复制起点相关的复合体,是DNA聚合酶起点关联所必需的。7)与Dpb11形成复合物的Sld2在S期被磷酸化,这种磷酸化依赖于S- cdk的活性。只有磷酸化形式的Sld2与Dpb11形成复合体,这是进一步装载DNA聚合酶所必需的。因此,S-Cdk通过磷酸化Sld2来控制DNA复制的起始。综上所述,Dpb11与Sld蛋白一起起着将DNA聚合酶装载到复制起点的作用。进一步的分析将对DNA聚合酶的起源链有更清晰的认识。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoichiro Kamimura: "DNA helicase III of Saccharomyces cerevisiae, encoded by YER176w(HELI), highly unwinds covalently closed, circular DNA in the presence of a DNA topoisomerase and yRF-A."J.Biochem. 25. 236-244 (1999)
Yoichiro Kamimura:“由 YER176w(HELI) 编码的酿酒酵母 DNA 解旋酶 III,在 DNA 拓扑异构酶和 yRF-A 存在的情况下高度解旋共价闭合的环状 DNA。”J.Biochem。
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    0
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Hiroshi Masumoto: "Dpb11 controls the association between DNA polymerase α and ε and the autonomously replication sequence region of budding yeast."Molecular and Cellular Biology. 20. 2809-2817 (2000)
Hiroshi Masumoto:“Dpb11 控制 DNA 聚合酶 α 和 ε 与芽殖酵母自主复制序列区域之间的关联。”《分子与细胞生物学》20. 2809-2817 (2000)。
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    0
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Yoichiro Kamimura: "Sld3, which interacts with Cdc45(Sld4), functions for chromosomal DNA replications in Saccharomyces cerevisiae."The EMBO Journal. (in press).
Yoichiro Kamimura:“Sld3 与 Cdc45(Sld4) 相互作用,在酿酒酵母中发挥染色体 DNA 复制的作用。”EMBO 杂志。
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  • 影响因子:
    0
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  • 通讯作者:
Kamimura, Y., Tak, Y.-S., Sugino, A.and Araki, H.: "Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replication in Saccharomyces cerevisiae."EMBO J.. (in press). (2001)
Kamimura, Y.、Tak, Y.-S.、Sugino, A. 和 Araki, H.:“Sld3 与 Cdc45 (Sld4) 相互作用,在酿酒酵母中发挥染色体 DNA 复制的功能。”EMBO J..(in
  • DOI:
  • 发表时间:
  • 期刊:
  • 影响因子:
    0
  • 作者:
  • 通讯作者:
Yoichiro Kamimura: "Sld3, which interacts with Cdc45 (Sld4), functions for chromosomal DNA replications in Saccharomyces cerevisiae."The EMBO Journal. (in press).
Yoichiro Kamimura:“Sld3 与 Cdc45 (Sld4) 相互作用,在酿酒酵母中发挥染色体 DNA 复制的作用。”EMBO 杂志。
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ARAKI Hiroyuki其他文献

ARAKI Hiroyuki的其他文献

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{{ truncateString('ARAKI Hiroyuki', 18)}}的其他基金

Development of thrust protection method for buried pipe using gabion
石笼埋地管道推力防护方法的研制
  • 批准号:
    17K14723
  • 财政年份:
    2017
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Development of biochemical and fine structural analyses methods for higher order chromosome structure
开发高阶染色体结构的生化和精细结构分析方法
  • 批准号:
    26650010
  • 财政年份:
    2014
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
Molecular mechanism of the initiation in eukaryotic chromosomal DNA replication
真核染色体DNA复制起始的分子机制
  • 批准号:
    25251005
  • 财政年份:
    2013
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)
Development of phosphorus recovery system by using zeolite and hydrotalcite are used and conjugative regeneration of adsorbents
沸石和水滑石磷回收系统的开发及吸附剂的共轭再生
  • 批准号:
    23560646
  • 财政年份:
    2011
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanism and regulation of assembly and remodeling of proteins
蛋白质组装和重塑的分子机制和调控
  • 批准号:
    20227004
  • 财政年份:
    2008
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (S)
Regulatory mechanism of replication complex formation and relationship between the complex, checkpoints and cell division
复制复合物形成的调控机制及其与检查点和细胞分裂之间的关系
  • 批准号:
    17080008
  • 财政年份:
    2005
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research on Priority Areas
Molecular mechanism of assembly of replication proteins at replication origins in eukaryotes
真核生物复制起点组装复制蛋白的分子机制
  • 批准号:
    15207012
  • 财政年份:
    2003
  • 资助金额:
    $ 5.25万
  • 项目类别:
    Grant-in-Aid for Scientific Research (A)

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