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ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway

Author

Listed:
  • Sile F. Yang

    (University of Sydney)

  • Christopher B. Nelson

    (University of Sydney)

  • Jadon K. Wells

    (University of Sydney)

  • Madushan Fernando

    (University of Sydney)

  • Robert Lu

    (University of Sydney)

  • Joshua A. M. Allen

    (University of Sydney)

  • Lisa Malloy

    (University of Sydney)

  • Noa Lamm

    (University of Sydney)

  • Vincent J. Murphy

    (St Vincent’s Institute)

  • Joel P. Mackay

    (University of Sydney)

  • Andrew J. Deans

    (St Vincent’s Institute
    University of Melbourne)

  • Anthony J. Cesare

    (University of Sydney)

  • Alexander P. Sobinoff

    (University of Sydney)

  • Hilda A. Pickett

    (University of Sydney)

Abstract

The ATR-CHK1 DNA damage response pathway becomes activated by the exposure of RPA-coated single-stranded DNA (ssDNA) that forms as an intermediate during DNA damage and repair, and as a part of the replication stress response. Here, we identify ZNF827 as a component of the ATR-CHK1 kinase pathway. We demonstrate that ZNF827 is a ssDNA binding protein that associates with RPA through concurrent binding to ssDNA intermediates. These interactions are dependent on two clusters of C2H2 zinc finger motifs within ZNF827. We find that ZNF827 accumulates at stalled forks and DNA damage sites, where it activates ATR and promotes the engagement of homologous recombination-mediated DNA repair. Additionally, we demonstrate that ZNF827 depletion inhibits replication initiation and sensitizes cancer cells to the topoisomerase inhibitor topotecan, revealing ZNF827 as a therapeutic target within the DNA damage response pathway.

Suggested Citation

  • Sile F. Yang & Christopher B. Nelson & Jadon K. Wells & Madushan Fernando & Robert Lu & Joshua A. M. Allen & Lisa Malloy & Noa Lamm & Vincent J. Murphy & Joel P. Mackay & Andrew J. Deans & Anthony J. , 2024. "ZNF827 is a single-stranded DNA binding protein that regulates the ATR-CHK1 DNA damage response pathway," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-46578-0
    DOI: 10.1038/s41467-024-46578-0
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    References listed on IDEAS

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    1. Robert Lu & Julienne J. O’Rourke & Alexander P. Sobinoff & Joshua A. M. Allen & Christopher B. Nelson & Christopher G. Tomlinson & Michael Lee & Roger R. Reddel & Andrew J. Deans & Hilda A. Pickett, 2019. "The FANCM-BLM-TOP3A-RMI complex suppresses alternative lengthening of telomeres (ALT)," Nature Communications, Nature, vol. 10(1), pages 1-14, December.
    2. Luca Busino & Maddalena Donzelli & Massimo Chiesa & Daniele Guardavaccaro & Dvora Ganoth & N. Valerio Dorrello & Avram Hershko & Michele Pagano & Giulio F. Draetta, 2003. "Degradation of Cdc25A by β-TrCP during S phase and in response to DNA damage," Nature, Nature, vol. 426(6962), pages 87-91, November.
    3. Matteo De March & Nekane Merino & Susana Barrera-Vilarmau & Ramon Crehuet & Silvia Onesti & Francisco J. Blanco & Alfredo De Biasio, 2017. "Structural basis of human PCNA sliding on DNA," Nature Communications, Nature, vol. 8(1), pages 1-7, April.
    4. V. Pragathi Masamsetti & Ronnie Ren Jie Low & Ka Sin Mak & Aisling O’Connor & Chris D. Riffkin & Noa Lamm & Laure Crabbe & Jan Karlseder & David C. S. Huang & Makoto T. Hayashi & Anthony J. Cesare, 2019. "Replication stress induces mitotic death through parallel pathways regulated by WAPL and telomere deprotection," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    5. Luke A. Yates & Ricardo J. Aramayo & Nilisha Pokhrel & Colleen C. Caldwell & Joshua A. Kaplan & Rajika L. Perera & Maria Spies & Edwin Antony & Xiaodong Zhang, 2018. "A structural and dynamic model for the assembly of Replication Protein A on single-stranded DNA," Nature Communications, Nature, vol. 9(1), pages 1-14, December.
    6. Stephen P. Jackson & Jiri Bartek, 2009. "The DNA-damage response in human biology and disease," Nature, Nature, vol. 461(7267), pages 1071-1078, October.
    7. Dennis Kappei & Marion Scheibe & Maciej Paszkowski-Rogacz & Alina Bluhm & Toni Ingolf Gossmann & Sabrina Dietz & Mario Dejung & Holger Herlyn & Frank Buchholz & Matthias Mann & Falk Butter, 2017. "Phylointeractomics reconstructs functional evolution of protein binding," Nature Communications, Nature, vol. 8(1), pages 1-9, April.
    8. Bruno Silva & Richard Pentz & Ana Margarida Figueira & Rajika Arora & Yong Woo Lee & Charlotte Hodson & Harry Wischnewski & Andrew J. Deans & Claus M. Azzalin, 2019. "FANCM limits ALT activity by restricting telomeric replication stress induced by deregulated BLM and R-loops," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
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