The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
Replication fork stability confers chemoresistance in BRCA-deficient cells
Open accessAbstract
Cells deficient in the Brca1 and Brca2 genes have reduced capacity to repair DNA double-strand breaks by homologous recombination and consequently are hypersensitive to DNA-damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore homologous recombination activity at double-strand breaks. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARP inhibitors and cisplatin resistance is associated with replication fork protection in Brca2-deficient tumour cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of replication fork protection, highlighting the complexities by which tumour cells evade chemotherapeutic interventions and acquire drug resistance.
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Cites
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
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Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase
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53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
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Self-citationXRCC3 promotes homology-directed repair of DNA damage in mammalian cells
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Self-citationBRCA2 Is Required for Homology-Directed Repair of Chromosomal Breaks
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Cited by
The multifaceted roles of PARP1 in DNA repair and chromatin remodelling
Ray Chaudhuri, A., & Nussenzweig, A. (2017) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm.2017.53 · Cited by 1,786
Self-citationEndogenous DNA damage as a source of genomic instability in cancer
Tubbs, A., & Nussenzweig, A. (2017) · Cell · doi:10.1016/j.cell.2017.01.002 · Cited by 1,452
Self-citationState-of-the-art strategies for targeting the DNA damage response in cancer
Pilié, P. G., Tang, C., Mills, G. B., & Yap, T. A. (2019) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-018-0114-z · Cited by 1,189
A decade of clinical development of PARP inhibitors in perspective
Mateo, J., Lord, C. J., Serra, V., Tutt, A., Balmaña, J., Castroviejo-Bermejo, M., Cruz, C., Oaknin, A., Kaye, S. B., & de Bono, J. S. (2019) · Annals of Oncology · doi:10.1093/annonc/mdz192 · Cited by 743
“For example, BRCA2-mutant cells with loss of the MLL3/4 complex protein, were reported to become PARPi-resistant by fork protection through reduction of MRE11 recruitment to stalled forks [80].”
BackgroundPARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance
Rose, M., Burgess, J. T., O’Byrne, K., Richard, D. J., & Bolderson, E. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.564601 · Cited by 719
Metadata
- Authors
- Ray Chaudhuri, A., Callen, E., Ding, X., Gogola, E., Duarte, A. A., Lee, J.-E., Wong, N., Lafarga, V., Calvo, J. A., Panzarino, N. J., John, S., Day, A., Crespo, A. V., Shen, B., Starnes, L. M., Ruiter, J. R. D., Daniel, J. A., Konstantinopoulos, P. A., Cortez, D., Cantor, S. B., Fernandez-Capetillo, O., Ge, K., Jonkers, J., Rottenberg, S., Sharan, S. K., & Nussenzweig, A.
- Venue
- Nature
- Published
- 2016-07-20
- Volume
- 535
- Issue
- 7612
- Pages
- 382-387
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2476568892
- Cited by
- 930
- References
- 44
- FWCI
- 38.52
- Type
- journal article
- Language
- en
- Open access
- green
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- Ray Chaudhuri, A., Callen, E., Ding, X., Gogola, E., Duarte, A. A., Lee, J.-E., Wong, N., Lafarga, V., Calvo, J. A., Panzarino, N. J., John, S., Day, A., Crespo, A. V., Shen, B., Starnes, L. M., Ruiter, J. R. D., Daniel, J. A., Konstantinopoulos, P. A., Cortez, D., . . . Nussenzweig, A. (2016). Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature. https://doi.org/10.1038/nature18325
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
