IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33479-3.html
   My bibliography  Save this article

MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair

Author

Listed:
  • Xiao-Wen Yang

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Xiao-Peng Han

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • Chong Han

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

  • James London

    (The Ohio State University Wexner Medical Center)

  • Richard Fishel

    (The Ohio State University Wexner Medical Center
    The James Comprehensive Cancer Center)

  • Jiaquan Liu

    (University of Chinese Academy of Sciences, Chinese Academy of Sciences)

Abstract

Highly conserved MutS and MutL homologs operate as protein dimers in mismatch repair (MMR). MutS recognizes mismatched nucleotides forming ATP-bound sliding clamps, which subsequently load MutL sliding clamps that coordinate MMR excision. Several MMR models envision static MutS-MutL complexes bound to mismatched DNA via a positively charged cleft (PCC) located on the MutL N-terminal domains (NTD). We show MutL-DNA binding is undetectable in physiological conditions. Instead, MutS sliding clamps exploit the PCC to position a MutL NTD on the DNA backbone, likely enabling diffusion-mediated wrapping of the remaining MutL domains around the DNA. The resulting MutL sliding clamp enhances MutH endonuclease and UvrD helicase activities on the DNA, which also engage the PCC during strand-specific incision/excision. These MutS clamp-loader progressions are significantly different from the replication clamp-loaders that attach the polymerase processivity factors β-clamp/PCNA to DNA, highlighting the breadth of mechanisms for stably linking crucial genome maintenance proteins onto DNA.

Suggested Citation

  • Xiao-Wen Yang & Xiao-Peng Han & Chong Han & James London & Richard Fishel & Jiaquan Liu, 2022. "MutS functions as a clamp loader by positioning MutL on the DNA during mismatch repair," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33479-3
    DOI: 10.1038/s41467-022-33479-3
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33479-3
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-33479-3?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jiaquan Liu & Jeungphill Hanne & Brooke M. Britton & Jared Bennett & Daehyung Kim & Jong-Bong Lee & Richard Fishel, 2016. "Cascading MutS and MutL sliding clamps control DNA diffusion to activate mismatch repair," Nature, Nature, vol. 539(7630), pages 583-587, November.
    2. Jiaquan Liu & Ryanggeun Lee & Brooke M. Britton & James A. London & Keunsang Yang & Jeungphill Hanne & Jong-Bong Lee & Richard Fishel, 2019. "MutL sliding clamps coordinate exonuclease-independent Escherichia coli mismatch repair," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    3. Kyung Suk Lee & Hamza Balci & Haifeng Jia & Timothy M. Lohman & Taekjip Ha, 2013. "Direct imaging of single UvrD helicase dynamics on long single-stranded DNA," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
    4. Jonghyun Park & Yongmoon Jeon & Daekil In & Richard Fishel & Changill Ban & Jong-Bong Lee, 2010. "Single-Molecule Analysis Reveals the Kinetics and Physiological Relevance of MutL-ssDNA Binding," PLOS ONE, Public Library of Science, vol. 5(11), pages 1-8, November.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Zhi-Qiang Xu & Slobodan Jergic & Allen T. Y. Lo & Alok C. Pradhan & Simon H. J. Brown & James C. Bouwer & Harshad Ghodke & Peter J. Lewis & Gökhan Tolun & Aaron J. Oakley & Nicholas E. Dixon, 2024. "Structural characterisation of the complete cycle of sliding clamp loading in Escherichia coli," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Yanan Li & Chao Liu & Xinshuo Jia & Lulu Bi & Zhiyun Ren & Yilin Zhao & Xia Zhang & Lijuan Guo & Yanling Bao & Cong Liu & Wei Li & Bo Sun, 2024. "RPA transforms RNase H1 to a bidirectional exoribonuclease for processive RNA–DNA hybrid cleavage," Nature Communications, Nature, vol. 15(1), pages 1-12, December.

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhi-Qiang Xu & Slobodan Jergic & Allen T. Y. Lo & Alok C. Pradhan & Simon H. J. Brown & James C. Bouwer & Harshad Ghodke & Peter J. Lewis & Gökhan Tolun & Aaron J. Oakley & Nicholas E. Dixon, 2024. "Structural characterisation of the complete cycle of sliding clamp loading in Escherichia coli," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    2. Sean P. Carney & Wen Ma & Kevin D. Whitley & Haifeng Jia & Timothy M. Lohman & Zaida Luthey-Schulten & Yann R. Chemla, 2021. "Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    3. Lina Wang & Siru Li & Kai Wang & Na Wang & Qiaoling Liu & Zhen Sun & Li Wang & Lulu Wang & Quentin Liu & Chengli Song & Caigang Liu & Qingkai Yang, 2022. "DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance," Nature Communications, Nature, vol. 13(1), pages 1-18, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33479-3. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.