IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31415-z.html
   My bibliography  Save this article

WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage

Author

Listed:
  • Seong-Su Han

    (PennState Health Children’s Hospital
    University of Iowa Stead Family Children’s Hospital)

  • Kuo-Kuang Wen

    (PennState Health Children’s Hospital
    University of Iowa Stead Family Children’s Hospital)

  • María L. García-Rubio

    (University of Seville-CSIC-University Pablo de Olavide)

  • Marc S. Wold

    (University of Iowa Carver College of Medicine)

  • Andrés Aguilera

    (University of Seville-CSIC-University Pablo de Olavide)

  • Wojciech Niedzwiedz

    (The Institute of Cancer Research)

  • Yatin M. Vyas

    (PennState Health Children’s Hospital
    University of Iowa Stead Family Children’s Hospital)

Abstract

Perturbation in the replication-stress response (RSR) and DNA-damage response (DDR) causes genomic instability. Genomic instability occurs in Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disorder, yet the mechanism remains largely uncharacterized. Replication protein A (RPA), a single-strand DNA (ssDNA) binding protein, has key roles in the RSR and DDR. Here we show that human WAS-protein (WASp) modulates RPA functions at perturbed replication forks (RFs). Following genotoxic insult, WASp accumulates at RFs, associates with RPA, and promotes RPA:ssDNA complexation. WASp deficiency in human lymphocytes destabilizes RPA:ssDNA-complexes, impairs accumulation of RPA, ATR, ETAA1, and TOPBP1 at genotoxin-perturbed RFs, decreases CHK1 activation, and provokes global RF dysfunction. las17 (yeast WAS-homolog)-deficient S. cerevisiae also show decreased ScRPA accumulation at perturbed RFs, impaired DNA recombination, and increased frequency of DNA double-strand break (DSB)-induced single-strand annealing (SSA). Consequently, WASp (or Las17)-deficient cells show increased frequency of DSBs upon genotoxic insult. Our study reveals an evolutionarily conserved, essential role of WASp in the DNA stress-resolution pathway, such that WASp deficiency provokes RPA dysfunction-coupled genomic instability.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31415-z
    DOI: 10.1038/s41467-022-31415-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31415-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31415-z?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. Benjamin R. Schrank & Tomas Aparicio & Yinyin Li & Wakam Chang & Brian T. Chait & Gregg G. Gundersen & Max E. Gottesman & Jean Gautier, 2018. "Nuclear ARP2/3 drives DNA break clustering for homology-directed repair," Nature, Nature, vol. 559(7712), pages 61-66, July.
    2. 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. Jie Shi & Kristine Hauschulte & Ivan Mikicic & Srijana Maharjan & Valerie Arz & Tina Strauch & Jan B. Heidelberger & Jonas V. Schaefer & Birgit Dreier & Andreas Plückthun & Petra Beli & Helle D. Ulric, 2023. "Nuclear myosin VI maintains replication fork stability," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    2. 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.

    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. Baolei Yuan & Xuan Zhou & Keiichiro Suzuki & Gerardo Ramos-Mandujano & Mengge Wang & Muhammad Tehseen & Lorena V. Cortés-Medina & James J. Moresco & Sarah Dunn & Reyna Hernandez-Benitez & Tomoaki Hish, 2022. "Wiskott-Aldrich syndrome protein forms nuclear condensates and regulates alternative splicing," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    2. Camilla S. Colding-Christensen & Ellen S. Kakulidis & Javier Arroyo-Gomez & Ivo A. Hendriks & Connor Arkinson & Zita Fábián & Agnieszka Gambus & Niels Mailand & Julien P. Duxin & Michael L. Nielsen, 2023. "Profiling ubiquitin signalling with UBIMAX reveals DNA damage- and SCFβ-Trcp1-dependent ubiquitylation of the actin-organizing protein Dbn1," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Ying-Ying Jin & Peng Zhang & Le-Le Liu & Xiang Zhao & Xiao-Qing Hu & Si-Zhe Liu & Ze-Kun Li & Qian Liu & Jian-Qiao Wang & De-Long Hao & Zhu-Qin Zhang & Hou-Zao Chen & De-Pei Liu, 2024. "Enhancing homology-directed repair efficiency with HDR-boosting modular ssDNA donor," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    4. 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.
    5. Jie Shi & Kristine Hauschulte & Ivan Mikicic & Srijana Maharjan & Valerie Arz & Tina Strauch & Jan B. Heidelberger & Jonas V. Schaefer & Birgit Dreier & Andreas Plückthun & Petra Beli & Helle D. Ulric, 2023. "Nuclear myosin VI maintains replication fork stability," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    6. Ália dos Santos & Daniel E. Rollins & Yukti Hari-Gupta & Hannah McArthur & Mingxue Du & Sabrina Yong Zi Ru & Kseniia Pidlisna & Ane Stranger & Faeeza Lorgat & Danielle Lambert & Ian Brown & Kevin Howl, 2023. "Autophagy receptor NDP52 alters DNA conformation to modulate RNA polymerase II transcription," Nature Communications, Nature, vol. 14(1), pages 1-24, December.
    7. 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.
    8. 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.
    9. 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.
    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. 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:13:y:2022:i:1:d:10.1038_s41467-022-31415-z. 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.