The DOI matches its Crossref record; 60 of the 60 references it cites were found in a registry or an index.
DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity
Open accessAbstract
SUMMARY Repair of damaged DNA is essential for maintaining genome integrity and for preventing genome-instability-associated diseases, such as cancer. By combining proximity labeling with quantitative mass spectrometry, we generated high-resolution interaction neighborhood maps of the endogenously expressed DNA repair factors 53BP1, BRCA1, and MDC1. Our spatially resolved interaction maps reveal rich network intricacies, identify shared and bait-spe-cific interaction modules, and implicate previously concealed regulators in this process. We identified a novel vertebrate-specific protein complex, shieldin, comprising REV7 plus three previously unchar-acterized proteins, RINN1 (CTC-534A2.2), RINN2 (FAM35A), and RINN3 (C20ORF196). Recruitment of shieldin to DSBs, via the ATM-RNF8-RNF168–53BP1-RIF1 axis, promotes NHEJ-dependent repair of intrachromosomal breaks, immunoglobulin class-switch recombination (CSR), and fusion of unpro-tected telomeres. Shieldin functions as a downstream effector of 53BP1-RIF1 in restraining DNA end resec-tion and in sensitizing BRCA1-deficient cells to PARP inhibitors. These findings have implications for under-standing cancer-associated PARPi resistance and the evolution of antibody CSR in higher vertebrates.
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Cited by
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PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance
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Metadata
- Authors
- Gupta, R., Somyajit, K., Narita, T., Maskey, E., Stanlie, A., Kremer, M., Typas, D., Lammers, M., Mailand, N., Nussenzweig, A., Lukas, J., & Choudhary, C.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2018-05
- Volume
- 173
- Issue
- 4
- Pages
- 972-988.e23
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2798183676
- Cited by
- 469
- References
- 60
- FWCI
- 16.64
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Gupta, R., Somyajit, K., Narita, T., Maskey, E., Stanlie, A., Kremer, M., Typas, D., Lammers, M., Mailand, N., Nussenzweig, A., Lukas, J., & Choudhary, C. (2018). DNA Repair Network Analysis Reveals Shieldin as a Key Regulator of NHEJ and PARP Inhibitor Sensitivity. Cell. https://doi.org/10.1016/j.cell.2018.03.050
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