IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v13y2022i1d10.1038_s41467-022-32680-8.html
   My bibliography  Save this article

DAXX-ATRX regulation of p53 chromatin binding and DNA damage response

Author

Listed:
  • Nitish Gulve

    (The Wistar Institute)

  • Chenhe Su

    (The Wistar Institute)

  • Zhong Deng

    (The Wistar Institute)

  • Samantha S. Soldan

    (The Wistar Institute)

  • Olga Vladimirova

    (The Wistar Institute)

  • Jayamanna Wickramasinghe

    (The Wistar Institute)

  • Hongwu Zheng

    (Cornell University)

  • Andrew V. Kossenkov

    (The Wistar Institute)

  • Paul. M. Lieberman

    (The Wistar Institute)

Abstract

DAXX and ATRX are tumor suppressor proteins that form a histone H3.3 chaperone complex and are frequently mutated in cancers with the alternative lengthening of telomeres (ALT). Here, we show that DAXX and ATRX knock-out (KO) U87-T cells that have acquired ALT-like features have defects in p53 chromatin binding and DNA damage response. RNA-seq analysis revealed that p53 pathway is among the most perturbed. ChIP-seq and ATAC-seq revealed a genome-wide reduction in p53 DNA-binding and corresponding loss of chromatin accessibility at many p53 response elements across the genome. Both DAXX and ATRX null cells showed a depletion of histone H3.3 and accumulation of γH2AX at many p53 sites, including subtelomeres. These findings indicate that loss of DAXX or ATRX can compromise p53 chromatin binding and p53 DNA damage response in ALT-like cells, providing a link between histone composition, chromatin accessibility and tumor suppressor function of p53.

Suggested Citation

  • Nitish Gulve & Chenhe Su & Zhong Deng & Samantha S. Soldan & Olga Vladimirova & Jayamanna Wickramasinghe & Hongwu Zheng & Andrew V. Kossenkov & Paul. M. Lieberman, 2022. "DAXX-ATRX regulation of p53 chromatin binding and DNA damage response," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32680-8
    DOI: 10.1038/s41467-022-32680-8
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-022-32680-8
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-022-32680-8?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. Liangqian Huang & Trisha Agrawal & Guixin Zhu & Sixiang Yu & Liming Tao & JiaBei Lin & Ronen Marmorstein & James Shorter & Xiaolu Yang, 2021. "DAXX represents a new type of protein-folding enabler," Nature, Nature, vol. 597(7874), pages 132-137, September.
    2. Qingqing Yan & Phillip Wulfridge & John Doherty & Jose L. Fernandez-Luna & Pedro J. Real & Hsin-Yao Tang & Kavitha Sarma, 2022. "Proximity labeling identifies a repertoire of site-specific R-loop modulators," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    3. Yu-Ching Teng & Aishwarya Sundaresan & Ryan O’Hara & Vincent U. Gant & Minhua Li & Sara Martire & Jane N. Warshaw & Amrita Basu & Laura A. Banaszynski, 2021. "ATRX promotes heterochromatin formation to protect cells from G-quadruplex DNA-mediated stress," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Julia Truch & Damien J. Downes & Caroline Scott & E. Ravza Gür & Jelena M. Telenius & Emmanouela Repapi & Ron Schwessinger & Matthew Gosden & Jill M. Brown & Stephen Taylor & Pak Leng Cheong & Jim R. , 2022. "The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. David Clynes & Clare Jelinska & Barbara Xella & Helena Ayyub & Caroline Scott & Matthew Mitson & Stephen Taylor & Douglas R. Higgs & Richard J. Gibbons, 2015. "Suppression of the alternative lengthening of telomere pathway by the chromatin remodelling factor ATRX," Nature Communications, Nature, vol. 6(1), pages 1-11, 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. Iqbal Mahmud & Guimei Tian & Jia Wang & Tarun E. Hutchinson & Brandon J. Kim & Nikee Awasthee & Seth Hale & Chengcheng Meng & Allison Moore & Liming Zhao & Jessica E. Lewis & Aaron Waddell & Shangtao , 2023. "DAXX drives de novo lipogenesis and contributes to tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, 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. Courtney A Lovejoy & Kaori Takai & Michael S Huh & David J Picketts & Titia de Lange, 2020. "ATRX affects the repair of telomeric DSBs by promoting cohesion and a DAXX-dependent activity," PLOS Biology, Public Library of Science, vol. 18(1), pages 1-28, January.
    2. Ilaria Rosso & Corey Jones-Weinert & Francesca Rossiello & Matteo Cabrini & Silvia Brambillasca & Leonel Munoz-Sagredo & Zeno Lavagnino & Emanuele Martini & Enzo Tedone & Massimiliano Garre’ & Julio A, 2023. "Alternative lengthening of telomeres (ALT) cells viability is dependent on C-rich telomeric RNAs," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    3. Iqbal Mahmud & Guimei Tian & Jia Wang & Tarun E. Hutchinson & Brandon J. Kim & Nikee Awasthee & Seth Hale & Chengcheng Meng & Allison Moore & Liming Zhao & Jessica E. Lewis & Aaron Waddell & Shangtao , 2023. "DAXX drives de novo lipogenesis and contributes to tumorigenesis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    4. Julia Truch & Damien J. Downes & Caroline Scott & E. Ravza Gür & Jelena M. Telenius & Emmanouela Repapi & Ron Schwessinger & Matthew Gosden & Jill M. Brown & Stephen Taylor & Pak Leng Cheong & Jim R. , 2022. "The chromatin remodeller ATRX facilitates diverse nuclear processes, in a stochastic manner, in both heterochromatin and euchromatin," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    5. Timothy K. Turkalo & Antonio Maffia & Johannes J. Schabort & Samuel G. Regalado & Mital Bhakta & Marco Blanchette & Diana C. J. Spierings & Peter M. Lansdorp & Dirk Hockemeyer, 2023. "A non-genetic switch triggers alternative telomere lengthening and cellular immortalization in ATRX deficient cells," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Graeme J. Thorn & Christopher T. Clarkson & Anne Rademacher & Hulkar Mamayusupova & Gunnar Schotta & Karsten Rippe & Vladimir B. Teif, 2022. "DNA sequence-dependent formation of heterochromatin nanodomains," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    7. Sheng Chen & Anuradhika Puri & Braxton Bell & Joseph Fritsche & Hector H. Palacios & Maurie Balch & Macy L. Sprunger & Matthew K. Howard & Jeremy J. Ryan & Jessica N. Haines & Gary J. Patti & Albert A, 2024. "HTRA1 disaggregates α-synuclein amyloid fibrils and converts them into non-toxic and seeding incompetent species," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    8. Alice Mac Kain & Ghizlane Maarifi & Sophie-Marie Aicher & Nathalie Arhel & Artem Baidaliuk & Sandie Munier & Flora Donati & Thomas Vallet & Quang Dinh Tran & Alexandra Hardy & Maxime Chazal & François, 2022. "Identification of DAXX as a restriction factor of SARS-CoV-2 through a CRISPR/Cas9 screen," Nature Communications, Nature, vol. 13(1), pages 1-13, 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_s41467-022-32680-8. 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.