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Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods

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  • Melissa S Gildenberg
  • M Todd Washington

Abstract

Several pathways exist to bypass DNA damage during replication. One such pathway is template switching. The Rad5 protein plays two important roles in template switching: it is an E3 ubiquitin ligase that catalyzes PCNA poly-ubiquitylation and it is a helicase that converts replication forks to chicken foot structures. To understand the structure, conformational flexibility, and mechanism of Rad5, we used a full-ensemble hybrid method combining Langevin dynamics simulations and small-angle X-ray scattering. From these studies, we generated the first experimentally validated, high-resolution structural model of Rad5. We found that Rad5 is more compact and less extended than is suggested by its large amount of predicted intrinsic disorder. Thus, Rad5 likely has a novel intra-molecular interaction that limits the range of conformational space it can sample. We provide evidence for a novel interaction between the HIRAN and the helicase domains of Rad5, and we discuss the biological and mechanistic implications of this.

Suggested Citation

  • Melissa S Gildenberg & M Todd Washington, 2019. "Conformational flexibility of fork-remodeling helicase Rad5 shown by full-ensemble hybrid methods," PLOS ONE, Public Library of Science, vol. 14(10), pages 1-16, October.
    • Handle: RePEc:plo:pone00:0223875
    DOI: 10.1371/journal.pone.0223875
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    References listed on IDEAS

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    2. Sebastian Eustermann & Kevin Schall & Dirk Kostrewa & Kristina Lakomek & Mike Strauss & Manuela Moldt & Karl-Peter Hopfner, 2018. "Structural basis for ATP-dependent chromatin remodelling by the INO80 complex," Nature, Nature, vol. 556(7701), pages 386-390, April.
    3. Carsten Hoege & Boris Pfander & George-Lucian Moldovan & George Pyrowolakis & Stefan Jentsch, 2002. "RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO," Nature, Nature, vol. 419(6903), pages 135-141, September.
    4. Philipp Stelter & Helle D. Ulrich, 2003. "Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation," Nature, Nature, vol. 425(6954), pages 188-191, September.
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