Structure guided functional analysis of the S. cerevisiae Mre11 complex Journal Article

   


Authors: Hohl, M.; Yu, Y.; Kuryavyi, V.; Patel, D. J.; Petrini, J.
Article Title: Structure guided functional analysis of the S. cerevisiae Mre11 complex
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. © 2025 Elsevier B.V., All rights reserved.
Keywords: signal transduction; dna binding protein; genetics; mutation; dna-binding proteins; nonhuman; metabolism; dna damage; dna repair; signaling; protein; protein binding; mutational analysis; chemistry; dna; saccharomyces cerevisiae; dna breaks, double-stranded; dna damage response; double stranded dna break; models, molecular; saccharomyces cerevisiae proteins; adenosine triphosphate; saccharomyces cerevisiae protein; dna binding; hydrolysis; ultrastructure; fungus; molecular model; deoxyribonuclease; exodeoxyribonuclease; endodeoxyribonucleases; exodeoxyribonucleases; dna, fungal; cryoelectron microscopy; damage; fungal dna; article; mre11 protein, s cerevisiae; rad50 protein, s cerevisiae; xrs2 protein, s cerevisiae
Journal Title: Nature Communications
Volume: 16
ISSN: 2041-1723
Publisher: Nature Publishing Group  
Date Published: 2025-08-12
Start Page: 7469
Language: English
DOI: 10.1038/s41467-025-62583-3
PUBMED: 40796731
PROVIDER: scopus
PMCID: PMC12343972
DOI/URL:

https://www.scopus.com/inward/record.uri?eid=2-s2.0-105013038853&doi=10.1038%2Fs41467-025-62583-3&partnerID=40&md5=cdb51957705165974194bfd73af9554b
Notes: Article -- Source: Scopus
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MSK Authors
  1. John Petrini
    95 Petrini
  2. Marcel Hohl
    14 Hohl
  3. Dinshaw J Patel
    480 Patel
  4. Vitaly V Kuryavyi
    28 Kuryavyi
  5. You Yu
    9 Yu
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