IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32860-6.html
   My bibliography  Save this article

Rtt105 regulates RPA function by configurationally stapling the flexible domains

Author

Listed:
  • Sahiti Kuppa

    (Saint Louis University School of Medicine)

  • Jaigeeth Deveryshetty

    (Saint Louis University School of Medicine)

  • Rahul Chadda

    (Saint Louis University School of Medicine)

  • Jenna R. Mattice

    (Montana State University)

  • Nilisha Pokhrel

    (Marquette University
    Laronde Bio)

  • Vikas Kaushik

    (Saint Louis University School of Medicine)

  • Angela Patterson

    (Montana State University)

  • Nalini Dhingra

    (Memorial Sloan Kettering Cancer Center)

  • Sushil Pangeni

    (Johns Hopkins University)

  • Marisa K. Sadauskas

    (Saint Louis University School of Medicine)

  • Sajad Shiekh

    (Kent State University)

  • Hamza Balci

    (Kent State University)

  • Taekjip Ha

    (Johns Hopkins University
    Johns Hopkins University
    Howard Hughes Medical Institute)

  • Xiaolan Zhao

    (Memorial Sloan Kettering Cancer Center)

  • Brian Bothner

    (Montana State University)

  • Edwin Antony

    (Saint Louis University School of Medicine
    Marquette University)

Abstract

Replication Protein A (RPA) is a heterotrimeric complex that binds to single-stranded DNA (ssDNA) and recruits over three dozen RPA-interacting proteins to coordinate multiple aspects of DNA metabolism including DNA replication, repair, and recombination. Rtt105 is a molecular chaperone that regulates nuclear localization of RPA. Here, we show that Rtt105 binds to multiple DNA binding and protein-interaction domains of RPA and configurationally staples the complex. In the absence of ssDNA, Rtt105 inhibits RPA binding to Rad52, thus preventing spurious binding to RPA-interacting proteins. When ssDNA is available, Rtt105 promotes formation of high-density RPA nucleoprotein filaments and dissociates during this process. Free Rtt105 further stabilizes the RPA-ssDNA filaments by inhibiting the facilitated exchange activity of RPA. Collectively, our data suggest that Rtt105 sequesters free RPA in the nucleus to prevent untimely binding to RPA-interacting proteins, while stabilizing RPA-ssDNA filaments at DNA lesion sites.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32860-6
    DOI: 10.1038/s41467-022-32860-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32860-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32860-6?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. Thomas A. Guilliam & Nigel C. Brissett & Aaron Ehlinger & Benjamin A. Keen & Peter Kolesar & Elaine M. Taylor & Laura J. Bailey & Howard D. Lindsay & Walter J. Chazin & Aidan J. Doherty, 2017. "Molecular basis for PrimPol recruitment to replication forks by RPA," Nature Communications, Nature, vol. 8(1), pages 1-14, August.
    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. Sean R. Collins & Kyle M. Miller & Nancy L. Maas & Assen Roguev & Jeffrey Fillingham & Clement S. Chu & Maya Schuldiner & Marinella Gebbia & Judith Recht & Michael Shales & Huiming Ding & Hong Xu & Ju, 2007. "Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map," Nature, Nature, vol. 446(7137), pages 806-810, April.
    4. 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.
    5. Alexey Bochkarev & Richard A. Pfuetzner & Aled M. Edwards & Lori Frappier, 1997. "Structure of the single-stranded-DNA-binding domain of replication protein A bound to DNA," Nature, Nature, vol. 385(6612), pages 176-181, January.
    Full references (including those not matched with items on IDEAS)

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. 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.

    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. 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.
    2. 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.
    3. 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.
    4. 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.
    5. 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.
    6. 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.
    7. Aline Umuhire Juru & Rodolfo Ghirlando & Jinwei Zhang, 2024. "Structural basis of tRNA recognition by the widespread OB fold," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    8. Zhihua Kang & Pan Fu & Allen L. Alcivar & Haiqing Fu & Christophe Redon & Tzeh Keong Foo & Yamei Zuo & Caiyong Ye & Ryan Baxley & Advaitha Madireddy & Remi Buisson & Anja-Katrin Bielinsky & Lee Zou & , 2021. "BRCA2 associates with MCM10 to suppress PRIMPOL-mediated repriming and single-stranded gap formation after DNA damage," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    9. 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.
    10. 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.
    11. 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.
    12. 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.
    13. Seong-Su Han & Kuo-Kuang Wen & María L. García-Rubio & Marc S. Wold & Andrés Aguilera & Wojciech Niedzwiedz & Yatin M. Vyas, 2022. "WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Maria Dilia Palumbieri & Chiara Merigliano & Daniel González-Acosta & Danina Kuster & Jana Krietsch & Henriette Stoy & Thomas Känel & Svenja Ulferts & Bettina Welter & Joël Frey & Cyril Doerdelmann & , 2023. "Nuclear actin polymerization rapidly mediates replication fork remodeling upon stress by limiting PrimPol activity," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    15. 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.
    16. 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.
    17. Sameer Bikram Shah & Youhang Li & Shibo Li & Qing Hu & Tong Wu & Yanmeng Shi & Tran Nguyen & Isaac Ive & Linda Shi & Hailong Wang & Xiaohua Wu, 2024. "53BP1 deficiency leads to hyperrecombination using break-induced replication (BIR)," Nature Communications, Nature, vol. 15(1), pages 1-20, 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:13:y:2022:i:1:d:10.1038_s41467-022-32860-6. 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.