IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39579-y.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39579-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-023-39579-y?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    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.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Sahiti Kuppa & Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Nilisha Pokhrel & Vikas Kaushik & Angela Patterson & Nalini Dhingra & Sushil Pangeni & Marisa K. Sadauskas & Sajad Shiekh & Ham, 2022. "Rtt105 regulates RPA function by configurationally stapling the flexible domains," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Guangxue Liu & Jimin Li & Boxue He & Jiaqi Yan & Jingyu Zhao & Xuejie Wang & Xiaocong Zhao & Jingyan Xu & Yeyao Wu & Simin Zhang & Xiaoli Gan & Chun Zhou & Xiangpan Li & Xinghua Zhang & Xuefeng Chen, 2023. "Bre1/RNF20 promotes Rad51-mediated strand exchange and antagonizes the Srs2/FBH1 helicases," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Fritz Nagae & Yasuto Murayama & Tsuyoshi Terakawa, 2024. "Molecular mechanism of parental H3/H4 recycling at a replication fork," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. Clément Madru & Markel Martínez-Carranza & Sébastien Laurent & Alessandra C. Alberti & Maelenn Chevreuil & Bertrand Raynal & Ahmed Haouz & Rémy A. Meur & Marc Delarue & Ghislaine Henneke & Didier Flam, 2023. "DNA-binding mechanism and evolution of replication protein A," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    5. Lorena Espinar & Marta Garcia-Cao & Alisa Schmidt & Savvas Kourtis & Antoni Gañez Zapater & Carla Aranda-Vallejo & Ritobrata Ghose & Laura Garcia-Lopez & Ilir Sheraj & Natalia Pardo-Lorente & Marina B, 2024. "Nuclear IMPDH2 controls the DNA damage response by modulating PARP1 activity," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    6. Aditi Mukherjee & Zakir Hossain & Esteban Erben & Shuai Ma & Jun Yong Choi & Hee-Sook Kim, 2023. "Identification of a small-molecule inhibitor that selectively blocks DNA-binding by Trypanosoma brucei replication protein A1," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Sarah R. Hengel & Katherine G. Oppenheimer & Chelsea M. Smith & Matthew A. Schaich & Hayley L. Rein & Julieta Martino & Kristie E. Darrah & Maggie Witham & Oluchi C. Ezekwenna & Kyle R. Burton & Benne, 2024. "The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    8. Jaigeeth Deveryshetty & Rahul Chadda & Jenna R. Mattice & Simrithaa Karunakaran & Michael J. Rau & Katherine Basore & Nilisha Pokhrel & Noah Englander & James A. J. Fitzpatrick & Brian Bothner & Edwin, 2023. "Yeast Rad52 is a homodecamer and possesses BRCA2-like bipartite Rad51 binding modes," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    9. Ananya Acharya & Kristina Kasaciunaite & Martin Göse & Vera Kissling & Raphaël Guérois & Ralf Seidel & Petr Cejka, 2021. "Distinct RPA domains promote recruitment and the helicase-nuclease activities of Dna2," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    10. Poonam Roshan & Sahiti Kuppa & Jenna R. Mattice & Vikas Kaushik & Rahul Chadda & Nilisha Pokhrel & Brunda R. Tumala & Aparna Biswas & Brian Bothner & Edwin Antony & Sofia Origanti, 2023. "An Aurora B-RPA signaling axis secures chromosome segregation fidelity," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    11. Sile F. Yang & Christopher B. Nelson & Jadon K. Wells & Madushan Fernando & Robert Lu & Joshua A. M. Allen & Lisa Malloy & Noa Lamm & Vincent J. Murphy & Joel P. Mackay & Andrew J. Deans & Anthony J. , 2024. "ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    12. Jina Yu & Chunli Yan & Tanmoy Paul & Lucas Brewer & Susan E. Tsutakawa & Chi-Lin Tsai & Samir M. Hamdan & John A. Tainer & Ivaylo Ivanov, 2024. "Molecular architecture and functional dynamics of the pre-incision complex in nucleotide excision repair," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39579-y. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.