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Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse

Author

Listed:
  • Feng Guo

    (University of Pennsylvania School of Medicine)

  • Deshmukh N. Gopaul

    (University of Pennsylvania School of Medicine)

  • Gregory D. Van Duyne

    (University of Pennsylvania School of Medicine)

Abstract

During site-specific DNA recombination, which brings about genetic rearrangement in processes such as viral integration and excision and chromosomal segregation, recombinase enzymes recognize specific DNA sequences and catalyse the reciprocal exchange of DNA strands between these sites. The bacteriophage recombinase Cre catalyses site-specific recombination between two 34-base-pair loxP sites. The crystal structure at 2.4 Å resolution of Cre bound to a loxP substrate reveals an intermediate in the recombination reaction, in which a Cre molecule has cleaved the substrate to form a covalent 3′-phosphotyrosine linkage with the DNA. Four recombinases and two loxP sites form a synapsed structure in which the DNA resembles models of four-way Holliday-junction intermediates. The Cre–loxP complex challenges models of site-specific recombination that require large changes in quaternary structure. Subtle allosteric changes at the carboxy termini of the Cre subunits may instead coordinate the cleavage and strand-exchange reactions.

Suggested Citation

  • Feng Guo & Deshmukh N. Gopaul & Gregory D. Van Duyne, 1997. "Structure of Cre recombinase complexed with DNA in a site-specific recombination synapse," Nature, Nature, vol. 389(6646), pages 40-46, September.
    • Handle: RePEc:nat:nature:v:389:y:1997:i:6646:d:10.1038_37925
    DOI: 10.1038/37925
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    Cited by:

    1. Huiming Zhang & Xian Fu & Xuemei Gong & Yun Wang & Haolin Zhang & Yu Zhao & Yue Shen, 2022. "Systematic dissection of key factors governing recombination outcomes by GCE-SCRaMbLE," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Charlotte Cautereels & Jolien Smets & Jonas De Saeger & Lloyd Cool & Yanmei Zhu & Anna Zimmermann & Jan Steensels & Anton Gorkovskiy & Thomas B. Jacobs & Kevin J. Verstrepen, 2024. "Orthogonal LoxPsym sites allow multiplexed site-specific recombination in prokaryotic and eukaryotic hosts," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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