IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51595-0.html
   My bibliography  Save this article

The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA

Author

Listed:
  • Sarah R. Hengel

    (UPMC-Hillman Cancer Center
    Department of Biology)

  • Katherine G. Oppenheimer

    (UPMC-Hillman Cancer Center)

  • Chelsea M. Smith

    (UPMC-Hillman Cancer Center
    Department of Pathology and Laboratory Medicine)

  • Matthew A. Schaich

    (UPMC-Hillman Cancer Center)

  • Hayley L. Rein

    (UPMC-Hillman Cancer Center)

  • Julieta Martino

    (UPMC-Hillman Cancer Center
    GeneDx)

  • Kristie E. Darrah

    (Department of Biochemistry and Biophysics)

  • Maggie Witham

    (Department of Biology)

  • Oluchi C. Ezekwenna

    (Department of Biology)

  • Kyle R. Burton

    (Department of Biology)

  • Bennett Houten

    (UPMC-Hillman Cancer Center)

  • Maria Spies

    (Department of Biochemistry and Molecular Biology)

  • Kara A. Bernstein

    (UPMC-Hillman Cancer Center
    Department of Biochemistry and Biophysics)

Abstract

Templated DNA repair that occurs during homologous recombination and replication stress relies on RAD51. RAD51 activity is positively regulated by BRCA2 and the RAD51 paralogs. The Shu complex is a RAD51 paralog-containing complex consisting of SWSAP1, SWS1, and SPIDR. We demonstrate that SWSAP1-SWS1 binds RAD51, maintains RAD51 filament stability, and enables strand exchange. Using single-molecule confocal fluorescence microscopy combined with optical tweezers, we show that SWSAP1-SWS1 decorates RAD51 filaments proficient for homologous recombination. We also find SWSAP1-SWS1 enhances RPA diffusion on ssDNA. Importantly, we show human sgSWSAP1 and sgSWS1 knockout cells are sensitive to pharmacological inhibition of PARP and APE1. Lastly, we identify cancer variants in SWSAP1 that alter Shu complex formation. Together, we show that SWSAP1-SWS1 stimulates RAD51-dependent high-fidelity repair and may be an important new cancer therapeutic target.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51595-0
    DOI: 10.1038/s41467-024-51595-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51595-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-51595-0?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. Rohit Prakash & Thomas Sandoval & Florian Morati & Jennifer A. Zagelbaum & Pei-Xin Lim & Travis White & Brett Taylor & Raymond Wang & Emilie C. B. Desclos & Meghan R. Sullivan & Hayley L. Rein & Kara , 2021. "Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    2. Edwige B Garcin & Stéphanie Gon & Meghan R Sullivan & Gregory J Brunette & Anne De Cian & Jean-Paul Concordet & Carine Giovannangeli & Wilhelm G Dirks & Sonja Eberth & Kara A Bernstein & Rohit Prakash, 2019. "Differential Requirements for the RAD51 Paralogs in Genome Repair and Maintenance in Human Cells," PLOS Genetics, Public Library of Science, vol. 15(10), pages 1-29, October.
    3. Yashpal Rawal & Lijia Jia & Aviv Meir & Shuo Zhou & Hardeep Kaur & Eliza A. Ruben & Youngho Kwon & Kara A. Bernstein & Maria Jasin & Alexander B. Taylor & Sandeep Burma & Robert Hromas & Alexander V. , 2023. "Structural insights into BCDX2 complex function in homologous recombination," Nature, Nature, vol. 619(7970), pages 640-649, July.
    4. Luke A. Greenhough & Chih-Chao Liang & Ondrej Belan & Simone Kunzelmann & Sarah Maslen & Monica C. Rodrigo-Brenni & Roopesh Anand & Mark Skehel & Simon J. Boulton & Stephen C. West, 2023. "Structure and function of the RAD51B–RAD51C–RAD51D–XRCC2 tumour suppressor," Nature, Nature, vol. 619(7970), pages 650-657, July.
    5. Kenichiro Matsuzaki & Shizuka Kondo & Tatsuya Ishikawa & Akira Shinohara, 2019. "Human RAD51 paralogue SWSAP1 fosters RAD51 filament by regulating the anti-recombinase FIGNL1 AAA+ ATPase," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    6. 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.
    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. Akbar Zainu & Pauline Dupaigne & Soumya Bouchouika & Julien Cau & Julie A. J. Clément & Pauline Auffret & Virginie Ropars & Jean-Baptiste Charbonnier & Bernard Massy & Raphael Mercier & Rajeev Kumar &, 2024. "FIGNL1-FIRRM is essential for meiotic recombination and prevents DNA damage-independent RAD51 and DMC1 loading," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. 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.
    3. 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.
    4. Rohit Prakash & Thomas Sandoval & Florian Morati & Jennifer A. Zagelbaum & Pei-Xin Lim & Travis White & Brett Taylor & Raymond Wang & Emilie C. B. Desclos & Meghan R. Sullivan & Hayley L. Rein & Kara , 2021. "Distinct pathways of homologous recombination controlled by the SWS1–SWSAP1–SPIDR complex," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    5. 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.
    6. Jessica D. Tischler & Hiroshi Tsuchida & Rosevalentine Bosire & Tommy T. Oda & Ana Park & Richard O. Adeyemi, 2024. "FLIP(C1orf112)-FIGNL1 complex regulates RAD51 chromatin association to promote viability after replication stress," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    7. 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.
    8. Masaru Ito & Asako Furukohri & Kenichiro Matsuzaki & Yurika Fujita & Atsushi Toyoda & Akira Shinohara, 2023. "FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    9. 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.
    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. 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.
    12. 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.
    13. 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.
    14. 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.
    15. 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:15:y:2024:i:1:d:10.1038_s41467-024-51595-0. 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.