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DNA repair

POLQ to the rescue for double-strand break repair during mitosis

Nature Structural & Molecular Biology volume 30, pages 1828–1830 (2023)Cite this article

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DNA polymerase θ (POLQ) repairs mitotic DNA breaks; this requires RHINO and PLK1, averts genomic instability and may underlie effects of POLQ inhibitors in HDR-deficient cancer cells. We discuss recent work on mitotic DNA break processing and repair, the need for multiple DSB repair pathways and implications of therapeutic POLQ targeting in cancer.

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Fig. 1: Regulation of DSB repair in mitosis by POLQ.

References

  1. Zirkle, R. E. & Bloom, W. Science 117, 487–493 (1953).

    Article  CAS  PubMed  Google Scholar 

  2. Orthwein, A. et al. Science 344, 189–193 (2014).

    Article  CAS  PubMed  Google Scholar 

  3. van Vugt, M. A. T. M. et al. PLoS Biol. 8, e1000287 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  4. Giunta, S., Belotserkovskaya, R. & Jackson, S. P. J. Cell Biol. 190, 197–207 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ayoub, N. et al. Curr. Biol. 19, 1075–1085 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Leimbacher, P.-A. et al. Mol. Cell 74, 571–583 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Adam, S. et al. Nat. Cancer 2, 1357–1371 (2021).

    Article  CAS  PubMed  Google Scholar 

  8. De Marco Zompit, M. et al. Nat. Commun. 13, 4143 (2022).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Brambati, A. et al. Science 381, 653–660 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Gelot, C. et al. Nature 621, 415–422 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sfeir, A. & Symington, L. S. Trends Biochem. Sci. 40, 701–714 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Ramsden, D. A., Carvajal-Garcia, J. & Gupta, G. P. Nat. Rev. Mol. Cell Biol. 23, 125–140 (2022).

    Article  CAS  PubMed  Google Scholar 

  13. Roerink, S. F., van Schendel, R. & Tijsterman, M. Genome Res. 24, 954–962 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Kamp, J. A., van Schendel, R., Dilweg, I. W. & Tijsterman, M. Nat. Commun. 11, 3615 (2020).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Llorens-Agost, M. et al. Nat. Cell Biol. 23, 1095–1104 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Heijink, A. M. et al. Nat. Commun. 13, 6722 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Li, J., Bagge, J., Lisby, M., Nilsson, J. & Oestergaard, V. H. Preprint at bioRxiv https://doi.org/10.1101/2022.03.30.486397 (2023).

  18. Zatreanu, D. et al. Nat. Commun. 12, 3636 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Schoonen, P. M. et al. Nat. Commun. 8, 15981 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Bhowmick, R., Hickson, I. D. & Liu, Y. Mol. Cell https://doi.org/10.1016/j.molcel.2023.08.023 (2023).

    Article  PubMed  Google Scholar 

  21. Yousefzadeh, M. J. & Wood, R. D. DNA Repair 12, 1–9 (2013).

    Article  CAS  PubMed  Google Scholar 

  22. Shima, N. et al. Genetics 163, 1031–1040 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Schimmel, J., van Schendel, R., den Dunnen, J. T. & Tijsterman, M. Trends Genet. 35, 632–644 (2019).

    Article  CAS  PubMed  Google Scholar 

  24. Shima, N., Munroe, R. J. & Schimenti, J. C. Mol. Cell Biol. 24, 10381–10389 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

M.A.T.M.v.V. is supported by grants from the Netherlands Organization for Scientific Research (NWO-VICI 09150182110019) and the Dutch Cancer Society (KWF-12911/14516). M.T. is supported by grants from the Dutch Cancer Society (KWF-13905) and the Holland Proton Therapy Centre (2019020-PROTON-DDR).

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Authors and Affiliations

  1. Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

    Marcel A. T. M. van Vugt

  2. Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands

    Marcel Tijsterman

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  1. Marcel A. T. M. van Vugt
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  2. Marcel Tijsterman
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Correspondence to Marcel A. T. M. van Vugt or Marcel Tijsterman.

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Competing interests

M.A.T.M.v.V. has acted on the scientific advisory boards of Nodus Oncology and RepareTx.

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van Vugt, M.A.T.M., Tijsterman, M. POLQ to the rescue for double-strand break repair during mitosis. Nat Struct Mol Biol 30, 1828–1830 (2023). https://doi.org/10.1038/s41594-023-01168-4

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