Journal article
FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange
Molecular cell, v 71(4), pp 621-628
16 Aug 2018
PMID: 30057198
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
FANCA is a component of the Fanconi anemia (FA) core complex that activates DNA interstrand crosslink repair by monoubiquitination of FANCD2. Here, we report that purified FANCA protein catalyzes bidirectional single-strand annealing (SA) and strand exchange (SE) at a level comparable to RAD52, while a disease-causing FANCA mutant, F1263Δ, is defective in both activities. FANCG, which directly interacts with FANCA, dramatically stimulates its SA and SE activities. Alternatively, FANCB, which does not directly interact with FANCA, does not stimulate this activity. Importantly, five other patient-derived FANCA mutants also exhibit deficient SA and SE, suggesting that the biochemical activities of FANCA are relevant to the etiology of FA. A cell-based DNA double-strand break (DSB) repair assay demonstrates that FANCA plays a direct role in the single-strand annealing sub-pathway (SSA) of DSB repair by catalyzing SA, and this role is independent of the canonical FA pathway and RAD52.
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•FANCA catalyzes bidirectional single-strand annealing and strand exchange•FANCG stimulates FANCA-mediated strand annealing and strand exchange•Fanconi anemia patient-derived FANCA mutants are deficient in both activities•The single-strand annealing activity of FANCA plays a direct role in DSB repair
Benitez et al. report that FANCA biochemically catalyzes single-strand annealing and strand exchange. They find that the single-strand annealing activity of FANCA is relevant to the etiology of Fanconi anemia and responsible for its involvement in double-strand break repair, which is independent of the canonical FA pathway and RAD52.
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Details
- Title
- FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange
- Creators
- Anaid Benitez - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAWenjun Liu - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAAnna Palovcak - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAGuanying Wang - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAJaewon Moon - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAKevin An - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAAnna Kim - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAKevin Zheng - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAYu Zhang - Department of Medicine, University of Miami Miller School of Medicine, Miami, FL 33136, USAFeng Bai - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USAAlexander V Mazin - Department of Biochemistry & Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USAXin-Hai Pei - Department of Surgery, University of Miami Miller School of Medicine, Miami, FL 33136, USAFenghua Yuan - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USAYanbin Zhang - Department of Biochemistry & Molecular Biology, University of Miami Miller School of Medicine, Miami, FL 33136, USA
- Publication Details
- Molecular cell, v 71(4), pp 621-628
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000441745600014
- Scopus ID
- 2-s2.0-85053835778
- Other Identifier
- 991014878173504721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology