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BRCA1 functions in homologous recombination (HR) both up- and downstream of DNA end resection. However, in cells with 53BP1 gene knockout (KO), BRCA1 is dispensable for the initiation of resection, but whether BRCA1 activity is entirely redundant after end resection is unclear. Here, we found that 53bp1 KO rescued the embryonic viability of a Brca1ΔC/ΔC mouse model that harbors a stop codon in the coiled-coil domain. However, Brca1ΔC/ΔC;53bp1-/- mice were susceptible to tumor formation, lacked Rad51 foci, and were sensitive to PARP inhibitor (PARPi) treatment, indicative of suboptimal HR. Furthermore, BRCA1 mutant cancer cell lines were dependent on truncated BRCA1 proteins that retained the ability to interact with PALB2 for 53BP1 KO induced RAD51 foci and PARPi resistance. Our data suggest that the overall efficiency of 53BP1 loss of function induced HR may be BRCA1 mutation dependent. In the setting of 53BP1 KO, hypomorphic BRCA1 proteins are active downstream of end resection, promoting RAD51 loading and PARPi resistance.
Pubmed ID: 30257212 RIS Download
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Non-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsSoftware for single-cell flow cytometry analysis. Its functions include management, display, manipulation, analysis and publication of the data stream produced by flow and mass cytometers.
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis polyclonal secondary targets IgG (H+L)
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets IgG
View all literature mentionsThis polyclonal targets Rabbit IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets IgG (H+L)
View all literature mentionsThis unknown targets Mouse IgG (H+L)
View all literature mentionsThis polyclonal targets Histone H3
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View all literature mentionsThis polyclonal targets RPA2
View all literature mentionsThis monoclonal targets HA-Tag
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View all literature mentionsThis monoclonal targets GMNN monoclonal antibody (M01) clone 1A8
View all literature mentionsThis monoclonal targets BRCA1 (Ab-1) Mouse mAb (MS110)
View all literature mentionsThis monoclonal targets 53BP1 (p53 Binding Protein 1)
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View all literature mentionsMus musculus with name B6C3F1/J from IMSR.
View all literature mentionsMus musculus with name B6;129-Trp53bp1tm1Jc/J from IMSR.
View all literature mentionsCell line MCF-7 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line OVCAR-5 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line OVCAR-3 is a Cancer cell line with a species of origin Homo sapiens (Human)
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View all literature mentionsCell line UWB1.289 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line SUM149PT is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentionsCell line MDA-MB-231 is a Cancer cell line with a species of origin Homo sapiens (Human)
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