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RNAPII-dependent ATM signaling at collisions with replication forks

Author

Listed:
  • Elias Einig

    (University Hospital Tübingen)

  • Chao Jin

    (University Hospital Tübingen)

  • Valentina Andrioletti

    (University Hospital Tübingen
    enGenome S.R.L.)

  • Boris Macek

    (Eberhard Karls University of Tübingen)

  • Nikita Popov

    (University Hospital Tübingen)

Abstract

Deregulation of RNA Polymerase II (RNAPII) by oncogenic signaling leads to collisions of RNAPII with DNA synthesis machinery (transcription-replication conflicts, TRCs). TRCs can result in DNA damage and are thought to underlie genomic instability in tumor cells. Here we provide evidence that elongating RNAPII nucleates activation of the ATM kinase at TRCs to stimulate DNA repair. We show the ATPase WRNIP1 associates with RNAPII and limits ATM activation during unperturbed cell cycle. WRNIP1 binding to elongating RNAPII requires catalytic activity of the ubiquitin ligase HUWE1. Mutation of HUWE1 induces TRCs, promotes WRNIP1 dissociation from RNAPII and binding to the replisome, stimulating ATM recruitment and activation at RNAPII. TRCs and translocation of WRNIP1 are rapidly induced in response to hydroxyurea treatment to activate ATM and facilitate subsequent DNA repair. We propose that TRCs can provide a controlled mechanism for stalling of replication forks and ATM activation, instrumental in cellular response to replicative stress.

Suggested Citation

  • 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.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-40924-4
    DOI: 10.1038/s41467-023-40924-4
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    References listed on IDEAS

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    1. Ricardo Almeida & José Miguel Fernández-Justel & Cristina Santa-María & Jean-Charles Cadoret & Laura Cano-Aroca & Rodrigo Lombraña & Gonzalo Herranz & Alessandra Agresti & María Gómez, 2018. "Chromatin conformation regulates the coordination between DNA replication and transcription," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    2. Min Li & Xiaohua Xu & Chou-Wei Chang & Li Zheng & Binghui Shen & Yilun Liu, 2018. "SUMO2 conjugation of PCNA facilitates chromatin remodeling to resolve transcription-replication conflicts," Nature Communications, Nature, vol. 9(1), pages 1-16, December.
    3. Morgane Macheret & Thanos D. Halazonetis, 2018. "Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress," Nature, Nature, vol. 555(7694), pages 112-116, March.
    4. Panagiotis Kotsantis & Lara Marques Silva & Sarah Irmscher & Rebecca M. Jones & Lisa Folkes & Natalia Gromak & Eva Petermann, 2016. "Increased global transcription activity as a mechanism of replication stress in cancer," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    5. 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.
    6. Yongkang Yang & Haiquan Lu & Chelsey Chen & Yajing Lyu & Robert N. Cole & Gregg L. Semenza, 2022. "HIF-1 Interacts with TRIM28 and DNA-PK to release paused RNA polymerase II and activate target gene transcription in response to hypoxia," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Prasun Chakraborty & Kevin Hiom, 2021. "DHX9-dependent recruitment of BRCA1 to RNA promotes DNA end resection in homologous recombination," Nature Communications, Nature, vol. 12(1), pages 1-18, December.
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