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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: 2ziv, 2ziw, 2zix

Cited: 44 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.

Reviews - 2ziu mentioned but not cited (1)

  1. GEN1/Yen1 and the SLX4 complex: Solutions to the problem of Holliday junction resolution. Svendsen JM, Harper JW. Genes Dev 24 521-536 (2010)

Articles - 2ziu mentioned but not cited (3)

  1. 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)
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Reviews citing this publication (13)

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Articles citing this publication (27)

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  2. ATR Protects the Genome against R Loops through a MUS81-Triggered Feedback Loop. Matos DA, Zhang JM, Ouyang J, Nguyen HD, Genois MM, Zou L. Mol Cell 77 514-527.e4 (2020)
  3. Repeat expansions confer WRN dependence in microsatellite-unstable cancers. van Wietmarschen N, Sridharan S, Nathan WJ, Tubbs A, Chan EM, Callen E, Wu W, Belinky F, Tripathi V, Wong N, Foster K, Noorbakhsh J, Garimella K, Cruz-Migoni A, Sommers JA, Huang Y, Borah AA, Smith JT, Kalfon J, Kesten N, Fugger K, Walker RL, Dolzhenko E, Eberle MA, Hayward BE, Usdin K, Freudenreich CH, Brosh RM, West SC, McHugh PJ, Meltzer PS, Bass AJ, Nussenzweig A. Nature 586 292-298 (2020)
  4. Mus81-Mms4 functions as a single heterodimer to cleave nicked intermediates in recombinational DNA repair. Schwartz EK, Wright WD, Ehmsen KT, Evans JE, Stahlberg H, Heyer WD. Mol Cell Biol 32 3065-3080 (2012)
  5. The mismatch repair and meiotic recombination endonuclease Mlh1-Mlh3 is activated by polymer formation and can cleave DNA substrates in trans. Manhart CM, Ni X, White MA, Ortega J, Surtees JA, Alani E. PLoS Biol 15 e2001164 (2017)
  6. Crystal structure of RuvC resolvase in complex with Holliday junction substrate. Górecka KM, Komorowska W, Nowotny M. Nucleic Acids Res 41 9945-9955 (2013)
  7. Two distinct MUS81-EME1 complexes from Arabidopsis process Holliday junctions. Geuting V, Kobbe D, Hartung F, Dürr J, Focke M, Puchta H. Plant Physiol 150 1062-1071 (2009)
  8. Structure and Function of the Small MutS-Related Domain. Fukui K, Kuramitsu S. Mol Biol Int 2011 691735 (2011)
  9. A junction branch point adjacent to a DNA backbone nick directs substrate cleavage by Saccharomyces cerevisiae Mus81-Mms4. Ehmsen KT, Heyer WD. Nucleic Acids Res 37 2026-2036 (2009)
  10. DNA binding residues in the RQC domain of Werner protein are critical for its catalytic activities. Tadokoro T, Kulikowicz T, Dawut L, Croteau DL, Bohr VA. Aging (Albany NY) 4 417-429 (2012)
  11. Architecture and DNA recognition elements of the Fanconi anemia FANCM-FAAP24 complex. Coulthard R, Deans AJ, Swuec P, Bowles M, Costa A, West SC, McDonald NQ. Structure 21 1648-1658 (2013)
  12. Downregulation of Mus81 as a novel prognostic biomarker for patients with colorectal carcinoma. Wu F, Shirahata A, Sakuraba K, Kitamura Y, Goto T, Saito M, Ishibashi K, Kigawa G, Nemoto H, Sanada Y, Hibi K. Cancer Sci 102 472-477 (2011)
  13. Crystal structure of a Fanconi anemia-associated nuclease homolog bound to 5' flap DNA: basis of interstrand cross-link repair by FAN1. Gwon GH, Kim Y, Liu Y, Watson AT, Jo A, Etheridge TJ, Yuan F, Zhang Y, Kim Y, Carr AM, Cho Y. Genes Dev 28 2276-2290 (2014)
  14. AtGEN1 and AtSEND1, two paralogs in Arabidopsis, possess holliday junction resolvase activity. Bauknecht M, Kobbe D. Plant Physiol 166 202-216 (2014)
  15. The Mus81-Mms4 structure-selective endonuclease requires nicked DNA junctions to undergo conformational changes and bend its DNA substrates for cleavage. Mukherjee S, Wright WD, Ehmsen KT, Heyer WD. Nucleic Acids Res 42 6511-6522 (2014)
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  17. Junction resolving enzymes use multivalency to keep the Holliday junction dynamic. Zhou R, Yang O, Déclais AC, Jin H, Gwon GH, Freeman ADJ, Cho Y, Lilley DMJ, Ha T. Nat Chem Biol 15 269-275 (2019)
  18. Efficient second strand cleavage during Holliday junction resolution by RuvC requires both increased junction flexibility and an exposed 5' phosphate. Osman F, Gaskell L, Whitby MC. PLoS One 4 e5347 (2009)
  19. A winged helix domain in human MUS81 binds DNA and modulates the endonuclease activity of MUS81 complexes. Fadden AJ, Schalbetter S, Bowles M, Harris R, Lally J, Carr AM, McDonald NQ. Nucleic Acids Res 41 9741-9752 (2013)
  20. 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)
  21. Functional characterization of two SOS-regulated genes involved in mitomycin C resistance in Caulobacter crescentus. Lopes-Kulishev CO, Alves IR, Valencia EY, Pidhirnyj MI, Fernández-Silva FS, Rodrigues TR, Guzzo CR, Galhardo RS. DNA Repair (Amst) 33 78-89 (2015)
  22. Effect of EME1 exon variant Ile350Thr on risk and early onset of breast cancer in southern Chinese women. Zhao J, Liu L, Zhang A, Chen Q, Fang W, Zeng L, Lu J. J Biomed Res 27 193-201 (2013)
  23. Holliday junction resolution by At-HIGLE: an SLX1 lineage endonuclease from Arabidopsis thaliana with a novel in-built regulatory mechanism. Verma P, Kumari P, Negi S, Yadav G, Gaur V. Nucleic Acids Res 50 4630-4646 (2022)
  24. Expression of MUS81 Mediates the Sensitivity of Castration-Resistant Prostate Cancer to Olaparib. Gong L, Tang Y, Jiang L, Tang W, Luo S. J Immunol Res 2022 4065580 (2022)
  25. MUS81 cleaves TOP1-derived lesions and other DNA-protein cross-links. Marini V, Nikulenkov F, Samadder P, Juul S, Knudsen BR, Krejci L. BMC Biol 21 110 (2023)
  26. Structural and Functional Characterization of the Holliday Junction Resolvase RuvC from Deinococcus radiodurans. Qin C, Han W, Xu Y, Zhao Y, Xu H, Tian B, Wang L, Hua Y. Microorganisms 10 1160 (2022)
  27. The Glu69Asp Polymorphism of EME1 Gene is Associated with an Increased Risk of Hepatocellular Carcinoma in Guangxi Population, China. Wang Y, Huang X, Su Z, He J, Zhao N, Nie L, Tang Y, Zhao H, Nong Q. Int J Gen Med 15 7855-7866 (2022)


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