ArticleProceedings of the National Academy of Sciences of the United States of America2021
Improved RAD51 binders through motif shuffling based on the modularity of BRC repeats.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Moss BRCA2 lacking the canonical DNA-binding domain promotes homologous recombination and binds to DNA.Nucleic acids research · 2025Article
- Novel COVID-19 biomarkers identified through multi-omics data analysis: N-acetyl-4-O-acetylneuraminic acid, N-acetyl-L-alanine, N-acetyltriptophan, palmitoylcarnitine, and glycerol 1-myristate.Internal and emergency medicine · 2024Article
- DMC1 and RAD51 bind FxxA and FxPP motifs of BRCA2 via two separate interfaces.Nucleic acids research · 2024Article
- A recombinant approach for stapled peptide discovery yields inhibitors of the RAD51 recombinase.Chemical science · 2023Article
- Enabling technology and core theory of synthetic biology.Science China. Life sciences · 2023Review
- Ultrahigh-Throughput Enzyme Engineering and Discovery inChemical reviews · 2023Review
- Amino acid analysis as a method of discovering biomarkers for diagnosis of diabetes and its complications.Amino acids · 2023Review
- Divergent binding mode for a protozoan BRC repeat to RAD51.The Biochemical journal · 2022Article
- Role of BRCA2 DNA-binding and C-terminal domain in its mobility and conformation in DNA repair.eLife · 2021Article
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Authors and funding
10 authors.
Funding
Abstract
Exchanges of protein sequence modules support leaps in function unavailable through point mutations during evolution. Here we study the role of the two RAD51-interacting modules within the eight binding BRC repeats of BRCA2. We created 64 chimeric repeats by shuffling these modules and measured their binding to RAD51. We found that certain shuffled module combinations were stronger binders than any of the module combinations in the natural repeats. Surprisingly, the contribution from the two modules was poorly correlated with affinities of natural repeats, with a weak BRC8 repeat containing the most effective N-terminal module. The binding of the strongest chimera, BRC8-2, to RAD51 was improved by -2.4 kCal/mol compared to the strongest natural repeat, BRC4. A crystal structure of RAD51:BRC8-2 complex shows an improved interface fit and an extended β-hairpin in this repeat. BRC8-2 was shown to function in human cells, preventing the formation of nuclear RAD51 foci after ionizing radiation.
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