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ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics

Author

Listed:
  • Jiawei Ding

    (Peking University)

  • Xiangting Li

    (University of California)

  • Jiangchuan Shen

    (Indiana University)

  • Yiling Zhao

    (Peking University
    Peking University Health Science Center)

  • Shuchen Zhong

    (Peking University)

  • Luhua Lai

    (Peking University
    Peking University)

  • Hengyao Niu

    (Indiana University)

  • Zhi Qi

    (Peking University)

Abstract

The eukaryotic single-stranded DNA (ssDNA)-binding protein Replication Protein A (RPA) plays a crucial role in various DNA metabolic pathways, including DNA replication and repair, by dynamically associating with ssDNA. While the binding of a single RPA molecule to ssDNA has been thoroughly studied, the accessibility of ssDNA is largely governed by the bimolecular behavior of RPA, the biophysical nature of which remains unclear. In this study, we develop a three-step low-complexity ssDNA Curtains method, which, when combined with biochemical assays and a Markov chain model in non-equilibrium physics, allow us to decipher the dynamics of multiple RPA binding to long ssDNA. Interestingly, our results suggest that Rad52, the mediator protein, can modulate the ssDNA accessibility of Rad51, which is nucleated on RPA coated ssDNA through dynamic ssDNA exposure between neighboring RPA molecules. We find that this process is controlled by the shifting between the protection mode and action mode of RPA ssDNA binding, where tighter RPA spacing and lower ssDNA accessibility are favored under RPA protection mode, which can be facilitated by the Rfa2 WH domain and inhibited by Rad52 RPA interaction.

Suggested Citation

  • Jiawei Ding & Xiangting Li & Jiangchuan Shen & Yiling Zhao & Shuchen Zhong & Luhua Lai & Hengyao Niu & Zhi Qi, 2023. "ssDNA accessibility of Rad51 is regulated by orchestrating multiple RPA dynamics," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39579-y
    DOI: 10.1038/s41467-023-39579-y
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    References listed on IDEAS

    as
    1. Jiangchuan Shen & Yiling Zhao & Nhung Tuyet Pham & Yuxi Li & Yixiang Zhang & Jonathan Trinidad & Grzegorz Ira & Zhi Qi & Hengyao Niu, 2022. "Deciphering the mechanism of processive ssDNA digestion by the Dna2-RPA ensemble," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Luke A. Yates & Ricardo J. Aramayo & Nilisha Pokhrel & Colleen C. Caldwell & Joshua A. Kaplan & Rajika L. Perera & Maria Spies & Edwin Antony & Xiaodong Zhang, 2018. "A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    3. James H. New & Tomohiko Sugiyama & Elena Zaitseva & Stephen C. Kowalczykowski, 1998. "Rad52 protein stimulates DNA strand exchange by Rad51 and replication protein A," Nature, Nature, vol. 391(6665), pages 407-410, January.
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