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Structure guided functional analysis of the S. cerevisiae Mre11 complex

Author

Listed:
  • Marcel Hohl

    (Memorial Sloan-Kettering Cancer Center)

  • You Yu

    (Memorial Sloan-Kettering Cancer Center
    Zhejiang University
    Zhejiang University School of Medicine)

  • Vitaly Kuryavyi

    (Memorial Sloan-Kettering Cancer Center)

  • Dinshaw J. Patel

    (Memorial Sloan-Kettering Cancer Center)

  • John Petrini

    (Memorial Sloan-Kettering Cancer Center)

Abstract

The Mre11 complex comprises Mre11, Rad50 and Nbs1 (Xrs2 in S. cerevisiae). The core components, Mre11 and Rad50 are highly conserved, with readily identifiable orthologs in all clades of life, whereas Nbs1/Xrs2 are present only in eukaryotes. In eukaryotes, the complex is integral to the DNA damage response, acting in DNA double strand break (DSB) detection and repair, and the activation of DNA damage signaling. We present here a 3.2 Å cryo-EM structure of the S. cerevisiae Mre11-Rad50 complex with bound dsDNA. The structure provided a foundation for detailed mutational analyses regarding homo and heterotypic protein interfaces, as well as DNA binding properties of Rad50. We define several conserved residues in Rad50 and Mre11 that are critical to complex assembly as well as for DNA binding. In addition, the data reveal that the Rad50 coiled coil domain influences ATP hydrolysis over long distances.

Suggested Citation

  • Marcel Hohl & You Yu & Vitaly Kuryavyi & Dinshaw J. Patel & John Petrini, 2025. "Structure guided functional analysis of the S. cerevisiae Mre11 complex," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62583-3
    DOI: 10.1038/s41467-025-62583-3
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    References listed on IDEAS

    as
    1. Hisashi Tatebe & Chew Theng Lim & Hiroki Konno & Kazuhiro Shiozaki & Akira Shinohara & Takayuki Uchihashi & Asako Furukohri, 2020. "Rad50 zinc hook functions as a constitutive dimerization module interchangeable with SMC hinge," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    2. Fernando Moreno-Herrero & Martijn de Jager & Nynke H. Dekker & Roland Kanaar & Claire Wyman & Cees Dekker, 2005. "Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon binding DNA," Nature, Nature, vol. 437(7057), pages 440-443, September.
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    Cited by:

    1. Yilan Fan & Filiz Kuybu & Hengjun Cui & Katja Lammens & Jia-Xuan Chen & Michael Kugler & Christophe Jung & Karl-Peter Hopfner, 2025. "Structural basis for DNA break sensing by human MRE11-RAD50-NBS1 and its regulation by telomeric factor TRF2," Nature Communications, Nature, vol. 16(1), pages 1-15, December.

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