IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-31329-w.html
   My bibliography  Save this article

DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II

Author

Listed:
  • Barbara Steurer

    (Erasmus University Medical Center)

  • Roel C. Janssens

    (Erasmus University Medical Center)

  • Marit E. Geijer

    (Erasmus University Medical Center)

  • Fernando Aprile-Garcia

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Bart Geverts

    (Erasmus MC)

  • Arjan F. Theil

    (Erasmus University Medical Center)

  • Barbara Hummel

    (Max Planck Institute of Immunobiology and Epigenetics)

  • Martin E. Royen

    (Erasmus MC)

  • Bastiaan Evers

    (The Netherlands Cancer Institute)

  • René Bernards

    (The Netherlands Cancer Institute)

  • Adriaan B. Houtsmuller

    (Erasmus MC)

  • Ritwick Sawarkar

    (Max Planck Institute of Immunobiology and Epigenetics
    University of Cambridge)

  • Jurgen Marteijn

    (Erasmus University Medical Center)

Abstract

The precise regulation of RNA Polymerase II (Pol II) transcription after genotoxic stress is crucial for proper execution of the DNA damage-induced stress response. While stalling of Pol II on transcription-blocking lesions (TBLs) blocks transcript elongation and initiates DNA repair in cis, TBLs additionally elicit a response in trans that regulates transcription genome-wide. Here we uncover that, after an initial elongation block in cis, TBLs trigger the genome-wide VCP-mediated proteasomal degradation of promoter-bound, P-Ser5-modified Pol II in trans. This degradation is mechanistically distinct from processing of TBL-stalled Pol II, is signaled via GSK3, and contributes to the TBL-induced transcription block, even in transcription-coupled repair-deficient cells. Thus, our data reveal the targeted degradation of promoter-bound Pol II as a critical pathway that allows cells to cope with DNA damage-induced transcription stress and enables the genome-wide adaptation of transcription to genotoxic stress.

Suggested Citation

  • Barbara Steurer & Roel C. Janssens & Marit E. Geijer & Fernando Aprile-Garcia & Bart Geverts & Arjan F. Theil & Barbara Hummel & Martin E. Royen & Bastiaan Evers & René Bernards & Adriaan B. Houtsmull, 2022. "DNA damage-induced transcription stress triggers the genome-wide degradation of promoter-bound Pol II," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31329-w
    DOI: 10.1038/s41467-022-31329-w
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-31329-w
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-022-31329-w?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. Maria Tresini & Daniël O. Warmerdam & Petros Kolovos & Loes Snijder & Mischa G. Vrouwe & Jeroen A. A. Demmers & Wilfred F. J. van IJcken & Frank G. Grosveld & René H. Medema & Jan H. J. Hoeijmakers & , 2015. "The core spliceosome as target and effector of non-canonical ATM signalling," Nature, Nature, vol. 523(7558), pages 53-58, July.
    2. Nicholas Kwiatkowski & Tinghu Zhang & Peter B. Rahl & Brian J. Abraham & Jessica Reddy & Scott B. Ficarro & Anahita Dastur & Arnaud Amzallag & Sridhar Ramaswamy & Bethany Tesar & Catherine E. Jenkins , 2014. "Targeting transcription regulation in cancer with a covalent CDK7 inhibitor," Nature, Nature, vol. 511(7511), pages 616-620, July.
    3. Marina E. Borisova & Andrea Voigt & Maxim A. X. Tollenaere & Sanjeeb Kumar Sahu & Thomas Juretschke & Nastasja Kreim & Niels Mailand & Chunaram Choudhary & Simon Bekker-Jensen & Masato Akutsu & Sebast, 2018. "p38-MK2 signaling axis regulates RNA metabolism after UV-light-induced DNA damage," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    4. Jun Xu & Indrajit Lahiri & Wei Wang & Adam Wier & Michael A. Cianfrocco & Jenny Chong & Alissa A. Hare & Peter B. Dervan & Frank DiMaio & Andres E. Leschziner & Dong Wang, 2017. "Structural basis for the initiation of eukaryotic transcription-coupled DNA repair," Nature, Nature, vol. 551(7682), pages 653-657, November.
    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. Yongchang Zhu & Xiping Zhang & Meng Gao & Yanchao Huang & Yuanqing Tan & Avital Parnas & Sizhong Wu & Delin Zhan & Sheera Adar & Jinchuan Hu, 2024. "Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II," Nature Communications, Nature, vol. 15(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. Austin Hsu & Qiming Duan & Daniel S. Day & Xin Luo & Sarah McMahon & Yu Huang & Zachary B. Feldman & Zhen Jiang & Tinghu Zhang & Yanke Liang & Michael Alexanian & Arun Padmanabhan & Jonathan D. Brown , 2022. "Targeting transcription in heart failure via CDK7/12/13 inhibition," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    2. Elias Einig & Chao Jin & Valentina Andrioletti & Boris Macek & Nikita Popov, 2023. "RNAPII-dependent ATM signaling at collisions with replication forks," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Yongchang Zhu & Xiping Zhang & Meng Gao & Yanchao Huang & Yuanqing Tan & Avital Parnas & Sizhong Wu & Delin Zhan & Sheera Adar & Jinchuan Hu, 2024. "Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    4. Jieqiong Zhang & Zhenhua Hu & Hwa Hwa Chung & Yun Tian & Kah Weng Lau & Zheng Ser & Yan Ting Lim & Radoslaw M. Sobota & Hwei Fen Leong & Benjamin Jieming Chen & Clarisse Jingyi Yeo & Shawn Ying Xuan T, 2023. "Dependency of NELF-E-SLUG-KAT2B epigenetic axis in breast cancer carcinogenesis," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Tengfei Wang & Shuxiang Shi & Yuanyuan Shi & Peipei Jiang & Ganlu Hu & Qinying Ye & Zhan Shi & Kexin Yu & Chenguang Wang & Guoping Fan & Suwen Zhao & Hanhui Ma & Alex C. Y. Chang & Zhi Li & Qian Bian , 2023. "Chemical-induced phase transition and global conformational reorganization of chromatin," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Victoria I. Cushing & Adrian F. Koh & Junjie Feng & Kaste Jurgaityte & Alexander Bondke & Sebastian H. B. Kroll & Marion Barbazanges & Bodo Scheiper & Ash K. Bahl & Anthony G. M. Barrett & Simak Ali &, 2024. "High-resolution cryo-EM of the human CDK-activating kinase for structure-based drug design," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    7. Diana A. Llerena Schiffmacher & Shun-Hsiao Lee & Katarzyna W. Kliza & Arjan F. Theil & Masaki Akita & Angela Helfricht & Karel Bezstarosti & Camila Gonzalo-Hansen & Haico Attikum & Matty Verlaan-de Vr, 2024. "The small CRL4CSA ubiquitin ligase component DDA1 regulates transcription-coupled repair dynamics," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    8. Seina Ohe & Yuji Kubota & Kiyoshi Yamaguchi & Yusuke Takagi & Junichiro Nashimoto & Hiroko Kozuka-Hata & Masaaki Oyama & Yoichi Furukawa & Mutsuhiro Takekawa, 2022. "ERK-mediated NELF-A phosphorylation promotes transcription elongation of immediate-early genes by releasing promoter-proximal pausing of RNA polymerase II," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    9. Chunli Yan & Thomas Dodd & Jina Yu & Bernice Leung & Jun Xu & Juntaek Oh & Dong Wang & Ivaylo Ivanov, 2021. "Mechanism of Rad26-assisted rescue of stalled RNA polymerase II in transcription-coupled repair," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    10. Thibault Houles & Geneviève Lavoie & Sami Nourreddine & Winnie Cheung & Éric Vaillancourt-Jean & Célia M. Guérin & Mathieu Bouttier & Benoit Grondin & Sichun Lin & Marc K. Saba-El-Leil & Stephane Ange, 2022. "CDK12 is hyperactivated and a synthetic-lethal target in BRAF-mutated melanoma," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    11. Jayden Sterling & Jennifer R. Baker & Adam McCluskey & Lenka Munoz, 2023. "Systematic literature review reveals suboptimal use of chemical probes in cell-based biomedical research," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    12. Xuan Zhang & Jun Xu & Jing Hu & Sitao Zhang & Yajing Hao & Dongyang Zhang & Hao Qian & Dong Wang & Xiang-Dong Fu, 2024. "Cockayne Syndrome Linked to Elevated R-Loops Induced by Stalled RNA Polymerase II during Transcription Elongation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    13. Athanasios Siametis & Kalliopi Stratigi & Despoina Giamaki & Georgia Chatzinikolaou & Alexia Akalestou-Clocher & Evi Goulielmaki & Brian Luke & Björn Schumacher & George A. Garinis, 2024. "Transcription stress at telomeres leads to cytosolic DNA release and paracrine senescence," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    14. Victoria O. Shender & Ksenia S. Anufrieva & Polina V. Shnaider & Georgij P. Arapidi & Marat S. Pavlyukov & Olga M. Ivanova & Irina K. Malyants & Grigory A. Stepanov & Evgenii Zhuravlev & Rustam H. Zig, 2024. "Therapy-induced secretion of spliceosomal components mediates pro-survival crosstalk between ovarian cancer cells," Nature Communications, Nature, vol. 15(1), pages 1-26, 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_s41467-022-31329-w. 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.