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Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair

Author

Listed:
  • Raphael Ceccaldi

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Jessica C. Liu

    (Dana-Farber Cancer Institute, Harvard Medical School
    Harvard Medical School
    Harvard University)

  • Ravindra Amunugama

    (Howard Hughes Medical Institute, Harvard Medical School)

  • Ildiko Hajdu

    (Howard Hughes Medical Institute, Brigham and Women’s Hospital)

  • Benjamin Primack

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Mark I. R. Petalcorin

    (DNA Damage Response Laboratory, Cancer Research UK, London Research Institute, Clare Hall, South Mimms EN6 3LD, UK)

  • Kevin W. O’Connor

    (Dana-Farber Cancer Institute, Harvard Medical School)

  • Panagiotis A. Konstantinopoulos

    (Medical Gynecologic Oncology Program, Dana-Farber Cancer Institute, Harvard Medical School)

  • Stephen J. Elledge

    (Howard Hughes Medical Institute, Brigham and Women’s Hospital)

  • Simon J. Boulton

    (DNA Damage Response Laboratory, Cancer Research UK, London Research Institute, Clare Hall, South Mimms EN6 3LD, UK)

  • Timur Yusufzai

    (Dana-Farber Cancer Institute, Harvard Medical School
    Harvard Medical School)

  • Alan D. D’Andrea

    (Dana-Farber Cancer Institute, Harvard Medical School)

Abstract

In studies in mammalian cells, polymerase theta (Polθ, also known as POLQ) is identified as the polymerase responsible for non-homologous end joining DNA repair; this DNA repair pathway acts in many tumours when homologous recombination is inactivated and the identification of the polymerase responsible may aid the development of new therapeutic approaches.

Suggested Citation

  • Raphael Ceccaldi & Jessica C. Liu & Ravindra Amunugama & Ildiko Hajdu & Benjamin Primack & Mark I. R. Petalcorin & Kevin W. O’Connor & Panagiotis A. Konstantinopoulos & Stephen J. Elledge & Simon J. B, 2015. "Homologous-recombination-deficient tumours are dependent on Polθ-mediated repair," Nature, Nature, vol. 518(7538), pages 258-262, February.
    • Handle: RePEc:nat:nature:v:518:y:2015:i:7538:d:10.1038_nature14184
    DOI: 10.1038/nature14184
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    Citations

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    Cited by:

    1. Anne Margriet Heijink & Colin Stok & David Porubsky & Eleni Maria Manolika & Jurrian K. Kanter & Yannick P. Kok & Marieke Everts & H. Rudolf Boer & Anastasia Audrey & Femke J. Bakker & Elles Wierenga , 2022. "Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    2. Fumiaki Ito & Ziyuan Li & Leonid Minakhin & Gurushankar Chandramouly & Mrityunjay Tyagi & Robert Betsch & John J. Krais & Bernadette Taberi & Umeshkumar Vekariya & Marissa Calbert & Tomasz Skorski & N, 2024. "Structural basis for a Polθ helicase small-molecule inhibitor revealed by cryo-EM," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    3. George E. Ronson & Katarzyna Starowicz & Elizabeth J. Anthony & Ann Liza Piberger & Lucy C. Clarke & Alexander J. Garvin & Andrew D. Beggs & Celina M. Whalley & Matthew J. Edmonds & James F. J. Beesle, 2023. "Mechanisms of synthetic lethality between BRCA1/2 and 53BP1 deficiencies and DNA polymerase theta targeting," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    4. Daniel J. Laverty & Shiv K. Gupta & Gary A. Bradshaw & Alexander S. Hunter & Brett L. Carlson & Nery Matias Calmo & Jiajia Chen & Shulan Tian & Jann N. Sarkaria & Zachary D. Nagel, 2024. "ATM inhibition exploits checkpoint defects and ATM-dependent double strand break repair in TP53-mutant glioblastoma," Nature Communications, Nature, vol. 15(1), pages 1-22, December.
    5. Megan E. Luedeman & Susanna Stroik & Wanjuan Feng & Adam J. Luthman & Gaorav P. Gupta & Dale A. Ramsden, 2022. "Poly(ADP) ribose polymerase promotes DNA polymerase theta-mediated end joining by activation of end resection," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    6. Yi-Li Feng & Qian Liu & Ruo-Dan Chen & Si-Cheng Liu & Zhi-Cheng Huang & Kun-Ming Liu & Xiao-Ying Yang & An-Yong Xie, 2022. "DNA nicks induce mutational signatures associated with BRCA1 deficiency," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    7. Jeffrey Patterson-Fortin & Heta Jadhav & Constantia Pantelidou & Tin Phan & Carter Grochala & Anita K. Mehta & Jennifer L. Guerriero & Gerburg M. Wulf & Brian M. Wolpin & Ben Z. Stanger & Andrew J. Ag, 2023. "RETRACTED ARTICLE: Polymerase θ inhibition activates the cGAS-STING pathway and cooperates with immune checkpoint blockade in models of BRCA-deficient cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    8. John J. Krais & David J. Glass & Ilse Chudoba & Yifan Wang & Wanjuan Feng & Dennis Simpson & Pooja Patel & Zemin Liu & Ryan Neumann-Domer & Robert G. Betsch & Andrea J. Bernhardy & Alice M. Bradbury &, 2023. "Genetic separation of Brca1 functions reveal mutation-dependent Polθ vulnerabilities," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    9. William Fried & Mrityunjay Tyagi & Leonid Minakhin & Gurushankar Chandramouly & Taylor Tredinnick & Mercy Ramanjulu & William Auerbacher & Marissa Calbert & Timur Rusanov & Trung Hoang & Nikita Boriso, 2024. "Discovery of a small-molecule inhibitor that traps Polθ on DNA and synergizes with PARP inhibitors," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    10. J. A. Kamp & B. B. L. G. Lemmens & R. J. Romeijn & S. C. Changoer & R. Schendel & M. Tijsterman, 2021. "Helicase Q promotes homology-driven DNA double-strand break repair and prevents tandem duplications," Nature Communications, Nature, vol. 12(1), pages 1-12, December.

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