The DOI matches its Crossref record; 30 of the 30 references it cites were found in a registry or an index.
REV7 counteracts DNA double-strand break resection and affects PARP inhibition
Open accessAbstract
Error-free repair of DNA double-strand breaks (DSBs) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway. In the absence of BRCA1-mediated HR, the administration of PARP inhibitors induces synthetic lethality of tumour cells of patients with breast or ovarian cancers. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases. In particular, little is known about BRCA1-independent restoration of HR. Here we show that loss of REV7 (also known as MAD2L2) in mouse and human cell lines re-establishes CTIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, which is reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX–MDC1–RNF8–RNF168–53BP1 chromatin pathway, and seems to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining during immunoglobulin class switch recombination. Our results reveal an unexpected crucial function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells.
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Cites
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Self-citation53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
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Human CtIP promotes DNA end resection
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Self-citationThe RIDDLE Syndrome Protein Mediates a Ubiquitin-Dependent Signaling Cascade at Sites of DNA Damage
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Cited by
Repair Pathway Choices and Consequences at the Double-Strand Break
Ceccaldi, R., Rondinelli, B., & D’Andrea, A. D. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.07.009 · Cited by 1,499
DNA double-strand break repair-pathway choice in somatic mammalian cells
Scully, R., Panday, A., Elango, R., & Willis, N. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0152-0 · Cited by 1,457
Lord, C. J., & Ashworth, A. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2015.21 · Cited by 1,257
Homologous Recombination Deficiency: Exploiting the Fundamental Vulnerability of Ovarian Cancer
Konstantinopoulos, P. A., Ceccaldi, R., Shapiro, G. I., & D'Andrea, A. D. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-0714 · Cited by 945
Targeting DNA damage response pathways in cancer
Groelly, F. J., Fawkes, M., Dagg, R. A., Blackford, A. N., & Tarsounas, M. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00535-5 · Cited by 836
Metadata
- Authors
- Xu, G., Chapman, J. R., Brandsma, I., Yuan, J., Mistrik, M., Bouwman, P., Bartkova, J., Gogola, E., Warmerdam, D., Barazas, M., Jaspers, J. E., Watanabe, K., Pieterse, M., Kersbergen, A., Sol, W., Celie, P. H. N., Schouten, P. C., van den Broek, B., Salman, A., Nieuwland, M., de Rink, I., de Ronde, J., Jalink, K., Boulton, S. J., Chen, J., van Gent, D. C., Bartek, J., Jonkers, J., Borst, P., & Rottenberg, S.
- Venue
- Nature
- Published
- 2015-03-23
- Volume
- 521
- Issue
- 7553
- Pages
- 541-544
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2058957446
- Cited by
- 593
- References
- 30
- FWCI
- 24.57
- Type
- journal article
- Language
- en
- Open access
- green
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- Xu, G., Chapman, J. R., Brandsma, I., Yuan, J., Mistrik, M., Bouwman, P., Bartkova, J., Gogola, E., Warmerdam, D., Barazas, M., Jaspers, J. E., Watanabe, K., Pieterse, M., Kersbergen, A., Sol, W., Celie, P. H. N., Schouten, P. C., van den Broek, B., Salman, A., . . . Rottenberg, S. (2015). REV7 counteracts DNA double-strand break resection and affects PARP inhibition. Nature. https://doi.org/10.1038/nature14328
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