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Crystal structure of the Mus81-Eme1 complex.

Chang JH, Kim JJ, Choi JM, Lee JH, Cho Y
Genes Dev 22 1093-106 (2008)
Related entries: 2ziu, 2ziv, 2ziw

Cited: 45 times
EuropePMC logo PMID: 18413719

Abstract

The Mus81-Eme1 complex is a structure-specific endonuclease that plays an important role in rescuing stalled replication forks and resolving the meiotic recombination intermediates in eukaryotes. We have determined the crystal structure of the Mus81-Eme1 complex. Both Mus81 and Eme1 consist of a central nuclease domain, two repeats of the helix-hairpin-helix (HhH) motif at their C-terminal region, and a linker helix. While each domain structure resembles archaeal XPF homologs, the overall structure is significantly different from those due to the structure of a linker helix. We show that a flexible intradomain linker that formed with 36 residues in the nuclease domain of Eme1 is essential for the recognition of DNA. We identified several basic residues lining the outer surface of the active site cleft of Mus81 that are involved in the interaction with a flexible arm of a nicked Holliday junction (HJ). These interactions might contribute to the optimal positioning of the opposite junction across the nick into the catalytic site, which provided the basis for the "nick and counternick" mechanism of Mus81-Eme1 and for the nicked HJ to be the favored in vitro substrate of this enzyme.

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  1. Automated minimization of steric clashes in protein structures. Ramachandran S, Kota P, Ding F, Dokholyan NV. Proteins 79 261-270 (2011)
  2. Crystal structures of the structure-selective nuclease Mus81-Eme1 bound to flap DNA substrates. Gwon GH, Jo A, Baek K, Jin KS, Fu Y, Lee JB, Kim Y, Cho Y. EMBO J 33 1061-1072 (2014)
  3. Computational Characterization of Small Molecules Binding to the Human XPF Active Site and Virtual Screening to Identify Potential New DNA Repair Inhibitors Targeting the ERCC1-XPF Endonuclease. Gentile F, Barakat KH, Tuszynski JA. Int J Mol Sci 19 E1328 (2018)
  4. Rapid and accurate structure-based therapeutic peptide design using GPU accelerated thermodynamic integration. Garton M, Corbi-Verge C, Hu Y, Nim S, Tarasova N, Sherborne B, Kim PM. Proteins 87 236-244 (2019)


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  1. Mechanisms of DNA damage, repair, and mutagenesis. Chatterjee N, Walker GC. Environ Mol Mutagen 58 235-263 (2017)
  2. Nucleases: diversity of structure, function and mechanism. Yang W. Q Rev Biophys 44 1-93 (2011)
  3. The Fanconi anemia DNA repair pathway: structural and functional insights into a complex disorder. Walden H, Deans AJ. Annu Rev Biophys 43 257-278 (2014)
  4. Processing of joint molecule intermediates by structure-selective endonucleases during homologous recombination in eukaryotes. Schwartz EK, Heyer WD. Chromosoma 120 109-127 (2011)
  5. Cruciform structures are a common DNA feature important for regulating biological processes. Brázda V, Laister RC, Jagelská EB, Arrowsmith C. BMC Mol Biol 12 33 (2011)
  6. Holliday junction resolvases. Wyatt HD, West SC. Cold Spring Harb Perspect Biol 6 a023192 (2014)
  7. GEN1/Yen1 and the SLX4 complex: Solutions to the problem of Holliday junction resolution. Svendsen JM, Harper JW. Genes Dev 24 521-536 (2010)
  8. A fine-scale dissection of the DNA double-strand break repair machinery and its implications for breast cancer therapy. Liu C, Srihari S, Cao KA, Chenevix-Trench G, Simpson PT, Ragan MA, Khanna KK. Nucleic Acids Res 42 6106-6127 (2014)
  9. Regulation of Structure-Specific Endonucleases in Replication Stress. Kim SM, Forsburg SL. Genes (Basel) 9 E634 (2018)
  10. Structural Aspects of DNA Repair and Recombination in Crop Improvement. Verma P, Tandon R, Yadav G, Gaur V. Front Genet 11 574549 (2020)
  11. Structure and mechanism of nucleases regulated by SLX4. Nowotny M, Gaur V. Curr Opin Struct Biol 36 97-105 (2016)
  12. Cell Cycle Regulation in Macrophages and Susceptibility to HIV-1. Ferreira IATM, Porterfield JZ, Gupta RK, Mlcochova P. Viruses 12 E839 (2020)
  13. Human MUS81: A Fence-Sitter in Cancer. Chen S, Geng X, Syeda MZ, Huang Z, Zhang C, Ying S. Front Cell Dev Biol 9 657305 (2021)
  14. DNA Holliday Junction: History, Regulation and Bioactivity. Song Q, Hu Y, Yin A, Wang H, Yin Q. Int J Mol Sci 23 9730 (2022)

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