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Search and processing of Holliday junctions within long DNA by junction-resolving enzymes

Author

Listed:
  • Artur P. Kaczmarczyk

    (Imperial College London
    MRC-London Institute of Medical Sciences)

  • Anne-Cécile Déclais

    (University of Dundee)

  • Matthew D. Newton

    (Imperial College London
    MRC-London Institute of Medical Sciences
    The Francis Crick Institute)

  • Simon J. Boulton

    (The Francis Crick Institute)

  • David M. J. Lilley

    (University of Dundee)

  • David S. Rueda

    (Imperial College London
    MRC-London Institute of Medical Sciences)

Abstract

Resolution of Holliday junctions is a critical intermediate step of homologous recombination in which junctions are processed by junction-resolving endonucleases. Although binding and cleavage are well understood, the question remains how the enzymes locate their substrate within long duplex DNA. Here we track fluorescent dimers of endonuclease I on DNA, presenting the complete single-molecule reaction trajectory for a junction-resolving enzyme finding and cleaving a Holliday junction. We show that the enzyme binds remotely to dsDNA and then undergoes 1D diffusion. Upon encountering a four-way junction, a catalytically-impaired mutant remains bound at that point. An active enzyme, however, cleaves the junction after a few seconds. Quantitative analysis provides a comprehensive description of the facilitated diffusion mechanism. We show that the eukaryotic junction-resolving enzyme GEN1 also undergoes facilitated diffusion on dsDNA until it becomes located at a junction, so that the general resolution trajectory is probably applicable to many junction resolving enzymes.

Suggested Citation

  • Artur P. Kaczmarczyk & Anne-Cécile Déclais & Matthew D. Newton & Simon J. Boulton & David M. J. Lilley & David S. Rueda, 2022. "Search and processing of Holliday junctions within long DNA by junction-resolving enzymes," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33503-6
    DOI: 10.1038/s41467-022-33503-6
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    References listed on IDEAS

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    1. Alfredo De Biasio & Alain Ibáñez de Opakua & Gulnahar B. Mortuza & Rafael Molina & Tiago N. Cordeiro & Francisco Castillo & Maider Villate & Nekane Merino & Sandra Delgado & David Gil-Cartón & Irene L, 2015. "Structure of p15PAF–PCNA complex and implications for clamp sliding during DNA replication and repair," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
    2. Leonard Wu & Ian D. Hickson, 2003. "The Bloom's syndrome helicase suppresses crossing over during homologous recombination," Nature, Nature, vol. 426(6968), pages 870-874, December.
    3. Jonathan M. Hadden & Anne-Cécile Déclais & Stephen B. Carr & David M. J. Lilley & Simon E. V. Phillips, 2007. "The structural basis of Holliday junction resolution by T7 endonuclease I," Nature, Nature, vol. 449(7162), pages 621-624, October.
    4. Christian Biertümpfel & Wei Yang & Dietrich Suck, 2007. "Crystal structure of T4 endonuclease VII resolving a Holliday junction," Nature, Nature, vol. 449(7162), pages 616-620, October.
    5. Géraldine Farge & Niels Laurens & Onno D. Broekmans & Siet M.J.L. van den Wildenberg & Linda C.M. Dekker & Martina Gaspari & Claes M. Gustafsson & Erwin J.G. Peterman & Maria Falkenberg & Gijs J.L. Wu, 2012. "Protein sliding and DNA denaturation are essential for DNA organization by human mitochondrial transcription factor A," Nature Communications, Nature, vol. 3(1), pages 1-9, January.
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