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.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Zirkle, R. E. & Bloom, W. Science 117, 487–493 (1953).
Orthwein, A. et al. Science 344, 189–193 (2014).
van Vugt, M. A. T. M. et al. PLoS Biol. 8, e1000287 (2010).
Giunta, S., Belotserkovskaya, R. & Jackson, S. P. J. Cell Biol. 190, 197–207 (2010).
Ayoub, N. et al. Curr. Biol. 19, 1075–1085 (2009).
Leimbacher, P.-A. et al. Mol. Cell 74, 571–583 (2019).
Adam, S. et al. Nat. Cancer 2, 1357–1371 (2021).
De Marco Zompit, M. et al. Nat. Commun. 13, 4143 (2022).
Brambati, A. et al. Science 381, 653–660 (2023).
Gelot, C. et al. Nature 621, 415–422 (2023).
Sfeir, A. & Symington, L. S. Trends Biochem. Sci. 40, 701–714 (2015).
Ramsden, D. A., Carvajal-Garcia, J. & Gupta, G. P. Nat. Rev. Mol. Cell Biol. 23, 125–140 (2022).
Roerink, S. F., van Schendel, R. & Tijsterman, M. Genome Res. 24, 954–962 (2014).
Kamp, J. A., van Schendel, R., Dilweg, I. W. & Tijsterman, M. Nat. Commun. 11, 3615 (2020).
Llorens-Agost, M. et al. Nat. Cell Biol. 23, 1095–1104 (2021).
Heijink, A. M. et al. Nat. Commun. 13, 6722 (2022).
Li, J., Bagge, J., Lisby, M., Nilsson, J. & Oestergaard, V. H. Preprint at bioRxiv https://doi.org/10.1101/2022.03.30.486397 (2023).
Zatreanu, D. et al. Nat. Commun. 12, 3636 (2021).
Schoonen, P. M. et al. Nat. Commun. 8, 15981 (2017).
Bhowmick, R., Hickson, I. D. & Liu, Y. Mol. Cell https://doi.org/10.1016/j.molcel.2023.08.023 (2023).
Yousefzadeh, M. J. & Wood, R. D. DNA Repair 12, 1–9 (2013).
Shima, N. et al. Genetics 163, 1031–1040 (2003).
Schimmel, J., van Schendel, R., den Dunnen, J. T. & Tijsterman, M. Trends Genet. 35, 632–644 (2019).
Shima, N., Munroe, R. J. & Schimenti, J. C. Mol. Cell Biol. 24, 10381–10389 (2004).
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).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
M.A.T.M.v.V. has acted on the scientific advisory boards of Nodus Oncology and RepareTx.
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41594-023-01168-4