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Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase

Author

Listed:
  • Sean P. Carney

    (University of Illinois at Urbana-Champaign)

  • Wen Ma

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    University of California)

  • Kevin D. Whitley

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign
    Newcastle University)

  • Haifeng Jia

    (Washington University in St. Louis School of Medicine)

  • Timothy M. Lohman

    (Washington University in St. Louis School of Medicine)

  • Zaida Luthey-Schulten

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

  • Yann R. Chemla

    (University of Illinois at Urbana-Champaign
    University of Illinois at Urbana-Champaign)

Abstract

UvrD, a model for non-hexameric Superfamily 1 helicases, utilizes ATP hydrolysis to translocate stepwise along single-stranded DNA and unwind the duplex. Previous estimates of its step size have been indirect, and a consensus on its stepping mechanism is lacking. To dissect the mechanism underlying DNA unwinding, we use optical tweezers to measure directly the stepping behavior of UvrD as it processes a DNA hairpin and show that UvrD exhibits a variable step size averaging ~3 base pairs. Analyzing stepping kinetics across ATP reveals the type and number of catalytic events that occur with different step sizes. These single-molecule data reveal a mechanism in which UvrD moves one base pair at a time but sequesters the nascent single strands, releasing them non-uniformly after a variable number of catalytic cycles. Molecular dynamics simulations point to a structural basis for this behavior, identifying the protein-DNA interactions responsible for strand sequestration. Based on structural and sequence alignment data, we propose that this stepping mechanism may be conserved among other non-hexameric helicases.

Suggested Citation

  • Sean P. Carney & Wen Ma & Kevin D. Whitley & Haifeng Jia & Timothy M. Lohman & Zaida Luthey-Schulten & Yann R. Chemla, 2021. "Kinetic and structural mechanism for DNA unwinding by a non-hexameric helicase," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-27304-6
    DOI: 10.1038/s41467-021-27304-6
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    References listed on IDEAS

    as
    1. Vitaly Epshtein & Venu Kamarthapu & Katelyn McGary & Vladimir Svetlov & Beatrix Ueberheide & Sergey Proshkin & Alexander Mironov & Evgeny Nudler, 2014. "UvrD facilitates DNA repair by pulling RNA polymerase backwards," Nature, Nature, vol. 505(7483), pages 372-377, January.
    2. Sophie Dumont & Wei Cheng & Victor Serebrov & Rudolf K. Beran & Ignacio Tinoco & Anna Marie Pyle & Carlos Bustamante, 2006. "RNA translocation and unwinding mechanism of HCV NS3 helicase and its coordination by ATP," Nature, Nature, vol. 439(7072), pages 105-108, January.
    3. Kyung Suk Lee & Hamza Balci & Haifeng Jia & Timothy M. Lohman & Taekjip Ha, 2013. "Direct imaging of single UvrD helicase dynamics on long single-stranded DNA," Nature Communications, Nature, vol. 4(1), pages 1-9, October.
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