IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-33535-y.html
   My bibliography  Save this article

ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress

Author

Listed:
  • Christopher P. Wardlaw

    (Memorial Sloan-Kettering Cancer Center)

  • John H. J. Petrini

    (Memorial Sloan-Kettering Cancer Center)

Abstract

The pathways involved in suppressing DNA replication stress and the associated DNA damage are critical to maintaining genome integrity. The Mre11 complex is unique among double strand break (DSB) repair proteins for its association with the DNA replication fork. Here we show that Mre11 complex inactivation causes DNA replication stress and changes in the abundance of proteins associated with nascent DNA. One of the most highly enriched proteins at the DNA replication fork upon Mre11 complex inactivation was the ubiquitin like protein ISG15. Mre11 complex deficiency and drug induced replication stress both led to the accumulation of cytoplasmic DNA and the subsequent activation of innate immune signaling via cGAS-STING-Tbk1. This led to ISG15 induction and protein ISGylation, including constituents of the replication fork. ISG15 plays a direct role in preventing replication stress. Deletion of ISG15 was associated with replication fork stalling, tonic ATR activation, genomic aberrations, and sensitivity to aphidicolin. These data reveal a previously unrecognized role for ISG15 in mitigating DNA replication stress and promoting genomic stability.

Suggested Citation

  • Christopher P. Wardlaw & John H. J. Petrini, 2022. "ISG15 conjugation to proteins on nascent DNA mitigates DNA replication stress," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33535-y
    DOI: 10.1038/s41467-022-33535-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-33535-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-33535-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. Karen J. Mackenzie & Paula Carroll & Carol-Anne Martin & Olga Murina & Adeline Fluteau & Daniel J. Simpson & Nelly Olova & Hannah Sutcliffe & Jacqueline K. Rainger & Andrea Leitch & Ruby T. Osborn & A, 2017. "cGAS surveillance of micronuclei links genome instability to innate immunity," Nature, Nature, vol. 548(7668), pages 461-465, August.
    2. Yifeng Zhang & Fabien Thery & Nicholas C. Wu & Emma K. Luhmann & Olivier Dussurget & Mariko Foecke & Clara Bredow & Daniel Jiménez-Fernández & Kevin Leandro & Antje Beling & Klaus-Peter Knobeloch & Fr, 2019. "The in vivo ISGylome links ISG15 to metabolic pathways and autophagy upon Listeria monocytogenes infection," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    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. Ramona N. Moro & Uddipta Biswas & Suhas S. Kharat & Filip D. Duzanic & Prosun Das & Maria Stavrou & Maria C. Raso & Raimundo Freire & Arnab Ray Chaudhuri & Shyam K. Sharan & Lorenza Penengo, 2023. "Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15," 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. Ramona N. Moro & Uddipta Biswas & Suhas S. Kharat & Filip D. Duzanic & Prosun Das & Maria Stavrou & Maria C. Raso & Raimundo Freire & Arnab Ray Chaudhuri & Shyam K. Sharan & Lorenza Penengo, 2023. "Interferon restores replication fork stability and cell viability in BRCA-defective cells via ISG15," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    2. Daipayan Banerjee & Kurt Langberg & Salar Abbas & Eric Odermatt & Praveen Yerramothu & Martin Volaric & Matthew A. Reidenbach & Kathy J. Krentz & C. Dustin Rubinstein & David L. Brautigan & Tarek Abba, 2021. "A non-canonical, interferon-independent signaling activity of cGAMP triggers DNA damage response signaling," Nature Communications, Nature, vol. 12(1), pages 1-24, December.
    3. Kate M. MacDonald & Shirony Nicholson-Puthenveedu & Maha M. Tageldein & Sarika Khasnis & Cheryl H. Arrowsmith & Shane M. Harding, 2023. "Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Cuige Zhu & Mari Iwase & Ziqian Li & Faliang Wang & Annabel Quinet & Alessandro Vindigni & Jieya Shao, 2022. "Profilin-1 regulates DNA replication forks in a context-dependent fashion by interacting with SNF2H and BOD1L," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    5. Yaping Huang & Changzheng Lu & Hanzhi Wang & Liya Gu & Yang-Xin Fu & Guo-Min Li, 2023. "DNAJA2 deficiency activates cGAS-STING pathway via the induction of aberrant mitosis and chromosome instability," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    6. Tanaz Sharifnia & Mathias J. Wawer & Amy Goodale & Yenarae Lee & Mariya Kazachkova & Joshua M. Dempster & Sandrine Muller & Joan Levy & Daniel M. Freed & Josh Sommer & Jérémie Kalfon & Francisca Vazqu, 2023. "Mapping the landscape of genetic dependencies in chordoma," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    7. Tomoko Yamamori Morita & Jie Yu & Yukie Kashima & Ryo Kamata & Gaku Yamamoto & Tatsunori Minamide & Chiaki Mashima & Miyuki Yoshiya & Yuta Sakae & Toyohiro Yamauchi & Yumi Hakozaki & Shun-ichiro Kagey, 2023. "CDC7 inhibition induces replication stress-mediated aneuploid cells with an inflammatory phenotype sensitizing tumors to immune checkpoint blockade," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    8. Lina Wang & Siru Li & Kai Wang & Na Wang & Qiaoling Liu & Zhen Sun & Li Wang & Lulu Wang & Quentin Liu & Chengli Song & Caigang Liu & Qingkai Yang, 2022. "DNA mechanical flexibility controls DNA potential to activate cGAS-mediated immune surveillance," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    9. Albert Stuart Reece & Gary Kenneth Hulse, 2022. "Cannabis- and Substance-Related Epidemiological Patterns of Chromosomal Congenital Anomalies in Europe: Geospatiotemporal and Causal Inferential Study," IJERPH, MDPI, vol. 19(18), pages 1-51, September.
    10. M. J. Gutbrod & B. Roche & J. I. Steinberg & A. A. Lakhani & K. Chang & A. J. Schorn & R. A. Martienssen, 2022. "Dicer promotes genome stability via the bromodomain transcriptional co-activator BRD4," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    11. Francesca Mateo & Zhengcheng He & Lin Mei & Gorka Ruiz de Garibay & Carmen Herranz & Nadia García & Amanda Lorentzian & Alexandra Baiges & Eline Blommaert & Antonio Gómez & Oriol Mirallas & Anna Garri, 2022. "Modification of BRCA1-associated breast cancer risk by HMMR overexpression," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    12. Jimyung Seo & HyunSeok Kim & Kyoung Il Min & Changgon Kim & Yongsoo Kwon & Zhenlong Zheng & Yusung Kim & Hyung-Soon Park & Young Seok Ju & Mi Ryung Roh & Kee Yang Chung & Joon Kim, 2022. "Weight-bearing activity impairs nuclear membrane and genome integrity via YAP activation in plantar melanoma," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    13. Yu-Hsuan Chen & Han-Hsiun Chen & Won-Jing Wang & Hsin-Yi Chen & Wei-Syun Huang & Chien-Han Kao & Sin-Rong Lee & Nai Yang Yeat & Ruei-Liang Yan & Shu-Jou Chan & Kuen-Phon Wu & Ruey-Hwa Chen, 2023. "TRABID inhibition activates cGAS/STING-mediated anti-tumor immunity through mitosis and autophagy dysregulation," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    14. Dario Zimmerli & Chiara S. Brambillasca & Francien Talens & Jinhyuk Bhin & Renske Linstra & Lou Romanens & Arkajyoti Bhattacharya & Stacey E. P. Joosten & Ana Moises Silva & Nuno Padrao & Max D. Welle, 2022. "MYC promotes immune-suppression in triple-negative breast cancer via inhibition of interferon signaling," Nature Communications, Nature, vol. 13(1), pages 1-18, 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_s41467-022-33535-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.