1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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Human Holliday junction resolvase GEN1 uses a chromodomain for efficient DNA recognition and cleavage

Research Article
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Cite this article as: eLife 2015;4:e12256 doi: 10.7554/eLife.12256

Abstract

Holliday junctions (HJs) are key DNA intermediates in homologous recombination. They link homologous DNA strands and have to be faithfully removed for proper DNA segregation and genome integrity. Here, we present the crystal structure of human HJ resolvase GEN1 complexed with DNA at 3.0 Å resolution. The GEN1 core is similar to other Rad2/XPG nucleases. However, unlike other members of the superfamily, GEN1 contains a chromodomain as an additional DNA interaction site. Chromodomains are known for their chromatin-targeting function in chromatin remodelers and histone(de)acetylases but they have not previously been found in nucleases. The GEN1 chromodomain directly contacts DNA and its truncation severely hampers GEN1's catalytic activity. Structure-guided mutations in vitroand in vivo in yeast validated our mechanistic findings. Our study provides the missing structure in the Rad2/XPG family and insights how a well-conserved nuclease core acquires versatility in recognizing diverse substrates for DNA repair and maintenance.

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Author details

  1. Shun-Hsiao Lee

    Department of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  2. Lissa Nicola Princz

    Department of Molecular Cell Biology, DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Maren Felizitas Klügel

    Department of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Bianca Habermann

    Computational Biology, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  5. Boris Pfander

    Department of Molecular Cell Biology, DNA Replication and Genome Integrity, Max Planck Institute of Biochemistry, Martinsried, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Christian Biertümpfel

    Department of Structural Cell Biology, Molecular Mechanisms of DNA Repair, Max Planck Institute of Biochemistry, Martinsried, Germany
    For correspondence
    biertuempfel@biochem.mpg.de
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Volker Dötsch, Goethe University, Germany

Publication history

  1. Received: October 12, 2015
  2. Accepted: December 17, 2015
  3. Accepted Manuscript published: December 18, 2015 (version 1)
  4. Version of Record published: September 27, 2016 (version 2)

Copyright

© 2015, Lee et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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