The DOI matches its Crossref record; 39 of the 39 references it cites were found in a registry or an index.
RETRACTED ARTICLE: A mechanism for the suppression of homologous recombination in G1 cells
Open accessAbstract
DNA repair by homologous recombination is highly suppressed in G1 cells to ensure that mitotic recombination occurs solely between sister chromatids. Although many homologous recombination factors are cell-cycle regulated, the identity of the events that are both necessary and sufficient to suppress recombination in G1 cells is unknown. Here we report that the cell cycle controls the interaction of BRCA1 with PALB2-BRCA2 to constrain BRCA2 function to the S/G2 phases in human cells. We found that the BRCA1-interaction site on PALB2 is targeted by an E3 ubiquitin ligase composed of KEAP1, a PALB2-interacting protein, in complex with cullin-3 (CUL3)-RBX1 (ref. 6). PALB2 ubiquitylation suppresses its interaction with BRCA1 and is counteracted by the deubiquitylase USP11, which is itself under cell cycle control. Restoration of the BRCA1-PALB2 interaction combined with the activation of DNA-end resection is sufficient to induce homologous recombination in G1, as measured by RAD51 recruitment, unscheduled DNA synthesis and a CRISPR-Cas9-based gene-targeting assay. We conclude that the mechanism prohibiting homologous recombination in G1 minimally consists of the suppression of DNA-end resection coupled with a multi-step block of the recruitment of BRCA2 to DNA damage sites that involves the inhibition of BRCA1-PALB2-BRCA2 complex assembly. We speculate that the ability to induce homologous recombination in G1 cells with defined factors could spur the development of gene-targeting applications in non-dividing cells.
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“because it is only readily available in dividing cells [110,111]”
From CRISPR-Cas: Converting A Bacterial Defence Mechanism into A State-of-the-Art Genetic Manipulation Tool (2019) · cites this paper as [111]
In the citing paper
“Non-mitotic cells are very inefficient for HDR-based repair, which is the main pathway to correct genetic disorders to date [87, 200].”
From Non-viral delivery systems for CRISPR/Cas9-based genome editing: challenges and opportunities (2018) · cites this paper as [200]
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Citations
Cites
1 retracted
Mitosis Inhibits DNA Double-Strand Break Repair to Guard Against Telomere Fusions
Orthwein, A., Fradet‐Turcotte, A., Noordermeer, S. M., Canny, M. D., Brun, C. M., Strecker, J., Escribano‐Diaz, C., & Durocher, D. (2014) · Science · doi:10.1126/science.1248024 · Cited by 332
Self-citationRetractedGenome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133
53BP1 Inhibits Homologous Recombination in Brca1-Deficient Cells by Blocking Resection of DNA Breaks
Bunting, S. F., Callén, E., Wong, N., Chen, H.-T., Polato, F., Gunn, A., Bothmer, A., Feldhahn, N., Fernandez-Capetillo, O., Cao, L., et al. (2010) · Cell · doi:10.1016/j.cell.2010.03.012 · Cited by 1,671
BRCA1 and BRCA2: different roles in a common pathway of genome protection
Roy, R., Chun, J., & Powell, S. N. (2011) · Nature reviews. Cancer · doi:10.1038/nrc3181 · Cited by 1,555
Defining the Human Deubiquitinating Enzyme Interaction Landscape
Sowa, M. E., Bennett, E. J., Gygi, S. P., & Harper, J. W. (2009) · Cell · doi:10.1016/j.cell.2009.04.042 · Cited by 1,523
Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution
Taguchi, K., Motohashi, H., & Yamamoto, M. (2011) · Genes to Cells · doi:10.1111/j.1365-2443.2010.01473.x · Cited by 1,478
Pathways of DNA Double-Strand Break Repair during the Mammalian Cell Cycle
Rothkamm, K., Krüger, I., Thompson, L. H., & Lübrich, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.16.5706-5715.2003 · Cited by 1,187
Repair of Strand Breaks by Homologous RecombinationPreprint
Jasin, M., & Rothstein, R. J. (2013) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a012740 · Cited by 929
Escribano‐Diaz, C., Orthwein, A., Fradet‐Turcotte, A., Xing, M., Young, J. T. F., Tkáč, J., Cook, M. A., Rosebrock, A. P., Munro, M., Canny, M. D., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.01.001 · Cited by 903
Self-citationControl of BRCA2 Cellular and Clinical Functions by a Nuclear Partner, PALB2
Xia, B., Sheng, Q., Nakanishi, K., Ohashi, A., Wu, J., Christ, N., Liu, X., Jasin, M., Couch, F. J., & Livingston, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.05.022 · Cited by 861
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Sorted by citations
ATM, ATR, and DNA-PK: The Trinity at the Heart of the DNA Damage Response
Blackford, A. N., & Jackson, S. P. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.05.015 · Cited by 2,050
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 1,542
In vivo genome editing via CRISPR/Cas9 mediated homology-independent targeted integration
Suzuki, K., Tsunekawa, Y., Hernandez-Benitez, R., Wu, J., Zhu, J., Kim, E. J., Hatanaka, F., Yamamoto, M., Araoka, T., Li, Z., et al. (2016) · Nature · doi:10.1038/nature20565 · Cited by 1,150
Deubiquitylating enzymes and drug discovery: emerging opportunities
Harrigan, J. A., Jacq, X., Martin, N. M., & Jackson, S. P. (2018) · Nature Reviews Drug Discovery · doi:10.1038/nrd.2017.152 · Cited by 940
Breaking the chains: deubiquitylating enzyme specificity begets function
Clague, M. J., Urbé, S., & Komander, D. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0099-1 · Cited by 878
Metadata
- Authors
- Orthwein, A., Noordermeer, S. M., Wilson, M. D., Landry, S., Enchev, R. I., Sherker, A., Munro, M., Pinder, J., Salsman, J., Dellaire, G., Xia, B., Peter, M., & Durocher, D.
- Affiliations
- Mount Sinai Hospital (CA)
- ETH Zurich (CH)
- Dalhousie University (CA)
- Rutgers, The State University of New Jersey (US)
- Corresponding author
- Durocher, Daniel
- ORCID
- Venue
- Nature
- Published
- 2015-12-09
- Volume
- 528
- Issue
- 7582
- Pages
- 422-426
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4880051
- OpenAlex
- W2202899490
- Cited by
- 471
- References
- 39
- Citations by year
- 2026: 4 · 2025: 17 · 2024: 26 · 2023: 35 · 2022: 36 · 2021: 52 · 2020: 61 · 2019: 64 · 2018: 52 · 2017: 67 · 2016: 54 · 2015: 1
- FWCI
- 25.17
- Type
- journal article
- Language
- en
- Status
- Retracted
- Update notices
- retraction (2025-01-27)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
- Funders
- Centers for Disease Control and Prevention
- Canadian Institutes of Health Research (FDN143343 (, MOP84260)
- National Cancer Institute (R01CA138804)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Oncology › PARP inhibition in cancer therapy
- Keywords
- homologous recombination, G1 cell cycle, BRCA1, PALB2, BRCA2, DNA end resection, cell cycle regulation, Keap1, CUL3, RBX1, USP11, ubiquitination, sister chromatid recombination, DNA repair, CRISPR/Cas9
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Fanconi Anemia Complementation Group N Protein, Amino Acid Sequence, Carrier Proteins, Cell Line, DNA, DNA Damage, DNA Repair, Humans, Molecular Sequence Data, Nuclear Proteins, Protein Binding, Thiolester Hydrolases, G1 Phase, G2 Phase, S Phase, Gene Targeting, BRCA1 Protein, BRCA2 Protein, Tumor Suppressor Proteins, Ubiquitin-Protein Ligases, Cullin Proteins, Multiprotein Complexes, Intracellular Signaling Peptides and Proteins, Rad51 Recombinase, Ubiquitination, Homologous Recombination, CRISPR-Cas Systems
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