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Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination

Author

Listed:
  • Pedro A. Mateos-Gomez

    (Skirball Institute of Biomolecular Medicine, NYU School of Medicine)

  • Fade Gong

    (Institute for Cellular and Molecular Biology, University of Texas at Austin. 2506 Speedway Stop A5000)

  • Nidhi Nair

    (The Scripps Research Institute)

  • Kyle M. Miller

    (Institute for Cellular and Molecular Biology, University of Texas at Austin. 2506 Speedway Stop A5000)

  • Eros Lazzerini-Denchi

    (The Scripps Research Institute)

  • Agnel Sfeir

    (Skirball Institute of Biomolecular Medicine, NYU School of Medicine)

Abstract

Next-generation sequencing technology is used to show that the error-prone polymerase θ (Polθ) is needed to promote alternative non-homologous end joining at telomeres, and during chromosomal translocations, while counteracting homologous recombination; inhibition of Polθ represents a potential therapeutic strategy for tumours that have mutations in homology-directed repair genes.

Suggested Citation

  • Pedro A. Mateos-Gomez & Fade Gong & Nidhi Nair & Kyle M. Miller & Eros Lazzerini-Denchi & Agnel Sfeir, 2015. "Mammalian polymerase θ promotes alternative NHEJ and suppresses recombination," Nature, Nature, vol. 518(7538), pages 254-257, February.
    • Handle: RePEc:nat:nature:v:518:y:2015:i:7538:d:10.1038_nature14157
    DOI: 10.1038/nature14157
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    Cited by:

    1. Sandra Wimberger & Nina Akrap & Mike Firth & Johan Brengdahl & Susanna Engberg & Marie K. Schwinn & Michael R. Slater & Anders Lundin & Pei-Pei Hsieh & Songyuan Li & Silvia Cerboni & Jonathan Sumner &, 2023. "Simultaneous inhibition of DNA-PK and Polϴ improves integration efficiency and precision of genome editing," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    2. Francesc Muyas & Manuel José Gómez Rodriguez & Rita Cascão & Angela Afonso & Carolin M. Sauer & Claudia C. Faria & Isidro Cortés-Ciriano & Ignacio Flores, 2024. "The ALT pathway generates telomere fusions that can be detected in the blood of cancer patients," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    3. 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.
    4. Juan A. Perez-Bermejo & Oghene Efagene & William M. Matern & Jeffrey K. Holden & Shaheen Kabir & Glen M. Chew & Gaia Andreoletti & Eniola Catton & Craig L. Ennis & Angelica Garcia & Trevor L. Gerstenb, 2024. "Functional screening in human HSPCs identifies optimized protein-based enhancers of Homology Directed Repair," Nature Communications, Nature, vol. 15(1), pages 1-16, 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. 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.
    7. Nikolaos Parisis & Pablo D. Dans & Muhammad Jbara & Balveer Singh & Diane Schausi-Tiffoche & Diego Molina-Serrano & Isabelle Brun-Heath & Denisa Hendrychová & Suman Kumar Maity & Diana Buitrago & Rafa, 2023. "Histone H3 serine-57 is a CHK1 substrate whose phosphorylation affects DNA repair," Nature Communications, Nature, vol. 14(1), pages 1-20, 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. Zhiqian Li & Lang You & Anita Hermann & Ethan Bier, 2024. "Developmental progression of DNA double-strand break repair deciphered by a single-allele resolution mutation classifier," Nature Communications, Nature, vol. 15(1), pages 1-19, December.

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