IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-51463-x.html
   My bibliography  Save this article

Coordination of transcription-coupled repair and repair-independent release of lesion-stalled RNA polymerase II

Author

Listed:
  • Yongchang Zhu

    (Fudan University)

  • Xiping Zhang

    (Fudan University)

  • Meng Gao

    (Fudan University)

  • Yanchao Huang

    (Fudan University)

  • Yuanqing Tan

    (Fudan University)

  • Avital Parnas

    (The Hebrew University of Jerusalem)

  • Sizhong Wu

    (Fudan University)

  • Delin Zhan

    (Fudan University)

  • Sheera Adar

    (The Hebrew University of Jerusalem)

  • Jinchuan Hu

    (Fudan University)

Abstract

Transcription-blocking lesions (TBLs) stall elongating RNA polymerase II (Pol II), which then initiates transcription-coupled repair (TCR) to remove TBLs and allow transcription recovery. In the absence of TCR, eviction of lesion-stalled Pol II is required for alternative pathways to address the damage, but the mechanism is unclear. Using Protein-Associated DNA Damage Sequencing (PADD-seq), this study reveals that the p97-proteasome pathway can evict lesion-stalled Pol II independently of repair. Both TCR and repair-independent eviction require CSA and ubiquitination. However, p97 is dispensable for TCR and Pol II eviction in TCR-proficient cells, highlighting repair’s prioritization over repair-independent eviction. Moreover, ubiquitination of RPB1-K1268 is important for both pathways, with USP7’s deubiquitinase activity promoting TCR without abolishing repair-independent Pol II release. In summary, this study elucidates the fate of lesion-stalled Pol II, and may shed light on the molecular basis of genetic diseases caused by the defects of TCR genes.

Suggested Citation

  • 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.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51463-x
    DOI: 10.1038/s41467-024-51463-x
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-51463-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-024-51463-x?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. 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.
    2. 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.
    3. Goran Kokic & Felix R. Wagner & Aleksandar Chernev & Henning Urlaub & Patrick Cramer, 2021. "Structural basis of human transcription–DNA repair coupling," Nature, Nature, vol. 598(7880), pages 368-372, October.
    4. Teresa A. Soucy & Peter G. Smith & Michael A. Milhollen & Allison J. Berger & James M. Gavin & Sharmila Adhikari & James E. Brownell & Kristine E. Burke & David P. Cardin & Stephen Critchley & Courtne, 2009. "An inhibitor of NEDD8-activating enzyme as a new approach to treat cancer," Nature, Nature, vol. 458(7239), pages 732-736, April.
    5. Lee Mulderrig & Juan I. Garaycoechea & Zewen K. Tuong & Christopher L. Millington & Felix A. Dingler & John R. Ferdinand & Liam Gaul & John A. Tadross & Mark J. Arends & Stephen O’Rahilly & Gerry P. C, 2021. "Aldehyde-driven transcriptional stress triggers an anorexic DNA damage response," Nature, Nature, vol. 600(7887), pages 158-163, 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. 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.
    2. 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.
    3. Jina Yu & Chunli Yan & Thomas Dodd & Chi-Lin Tsai & John A. Tainer & Susan E. Tsutakawa & Ivaylo Ivanov, 2023. "Dynamic conformational switching underlies TFIIH function in transcription and DNA repair and impacts genetic diseases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    4. Weize Wang & Ling Liang & Zonglin Dai & Peng Zuo & Shang Yu & Yishuo Lu & Dian Ding & Hongyi Chen & Hui Shan & Yan Jin & Youdong Mao & Yuxin Yin, 2024. "A conserved N-terminal motif of CUL3 contributes to assembly and E3 ligase activity of CRL3KLHL22," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    5. 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.
    6. María Arroyo & Florian D. Hastert & Andreas Zhadan & Florian Schelter & Susanne Zimbelmann & Cathia Rausch & Anne K. Ludwig & Thomas Carell & M. Cristina Cardoso, 2022. "Isoform-specific and ubiquitination dependent recruitment of Tet1 to replicating heterochromatin modulates methylcytosine oxidation," Nature Communications, Nature, vol. 13(1), pages 1-28, December.
    7. Ondrej Suchanek & John R. Ferdinand & Zewen K. Tuong & Sathi Wijeyesinghe & Anita Chandra & Ann-Katrin Clauder & Larissa N. Almeida & Simon Clare & Katherine Harcourt & Christopher J. Ward & Rachael B, 2023. "Tissue-resident B cells orchestrate macrophage polarisation and function," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    8. Debasish Paul & Stephen C. Kales & James A. Cornwell & Marwa M. Afifi & Ganesha Rai & Alexey Zakharov & Anton Simeonov & Steven D. Cappell, 2022. "Revealing β-TrCP activity dynamics in live cells with a genetically encoded biosensor," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Irineos Papakyriacou & Ginte Kutkaite & Marta Rúbies Bedós & Divya Nagarajan & Liam P. Alford & Michael P. Menden & Yumeng Mao, 2024. "Loss of NEDD8 in cancer cells causes vulnerability to immune checkpoint blockade in triple-negative breast cancer," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    10. Gang Xue & Jianing Xie & Matthias Hinterndorfer & Marko Cigler & Lara Dötsch & Hana Imrichova & Philipp Lampe & Xiufen Cheng & Soheila Rezaei Adariani & Georg E. Winter & Herbert Waldmann, 2023. "Discovery of a Drug-like, Natural Product-Inspired DCAF11 Ligand Chemotype," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    11. 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.
    12. Daewon Lee & Eunju Yoon & Su Jin Ham & Kunwoo Lee & Hansaem Jang & Daihn Woo & Da Hyun Lee & Sehyeon Kim & Sekyu Choi & Jongkyeong Chung, 2024. "Diabetic sensory neuropathy and insulin resistance are induced by loss of UCHL1 in Drosophila," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    13. Jiajun Tan & Yingfeng Li & Xiang Li & Xiaoxiao Zhu & Liping Liu & Hua Huang & Jiahua Wei & Hailing Wang & Yong Tian & Zhigao Wang & Zhuqiang Zhang & Bing Zhu, 2024. "Pramel15 facilitates zygotic nuclear DNMT1 degradation and DNA demethylation," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    14. Di Wu & Haomin Li & Mingwei Liu & Jun Qin & Yi Sun, 2022. "The Ube2m-Rbx1 neddylation-Cullin-RING-Ligase proteins are essential for the maintenance of Regulatory T cell fitness," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    15. Yilun Sun & Simone A. Baechler & Xiaohu Zhang & Suresh Kumar & Valentina M. Factor & Yasuhiro Arakawa & Cindy H. Chau & Kanako Okamoto & Anup Parikh & Bob Walker & Yijun P. Su & Jiji Chen & Tabitha Ti, 2023. "Targeting neddylation sensitizes colorectal cancer to topoisomerase I inhibitors by inactivating the DCAF13-CRL4 ubiquitin ligase complex," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    16. Cheng Xu & Hongyi Zhou & Yulan Jin & Khushboo Sahay & Anna Robicsek & Yisong Liu & Kunzhe Dong & Jiliang Zhou & Amanda Barrett & Huabo Su & Weiqin Chen, 2022. "Hepatic neddylation deficiency triggers fatal liver injury via inducing NF-κB-inducing kinase in mice," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    17. Binod Kumar & Natania S. Field & Dale D. Kim & Asif A. Dar & Yanqun Chen & Aishwarya Suresh & Christopher F. Pastore & Li-Yin Hung & Nadia Porter & Keisuke Sawada & Palak Shah & Omar Elbulok & Emily K, 2022. "The ubiquitin ligase Cul5 regulates CD4+ T cell fate choice and allergic inflammation," Nature Communications, Nature, vol. 13(1), pages 1-14, 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_s41467-024-51463-x. 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.