FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange

Anaid Benitez, Wenjun Liu, Anna Palovcak, Guanying Wang, Jaewon Moon, Kevin An, Anna Kim, Kevin Zheng, Yu Zhang, Feng Bai, Alexander V. Mazin, Xin-Hai Pei, Fenghua Yuan, Yanbin Zhang

Research output: Contribution to journalArticle

10 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)621-628.e4
JournalMolecular Cell
Volume71
Issue number4
DOIs
StatePublished - Aug 16 2018

Fingerprint

Fanconi Anemia
Double-Stranded DNA Breaks
Fanconi Anemia Complementation Group A Protein
DNA

Keywords

  • DNA double-strand break repair
  • FANCA
  • Fanconi anemia
  • single-strand annealing
  • strand exchange

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange. / Benitez, Anaid; Liu, Wenjun; Palovcak, Anna; Wang, Guanying; Moon, Jaewon; An, Kevin; Kim, Anna; Zheng, Kevin; Zhang, Yu; Bai, Feng; Mazin, Alexander V.; Pei, Xin-Hai; Yuan, Fenghua; Zhang, Yanbin.

In: Molecular Cell, Vol. 71, No. 4, 16.08.2018, p. 621-628.e4.

Research output: Contribution to journalArticle

Benitez, A, Liu, W, Palovcak, A, Wang, G, Moon, J, An, K, Kim, A, Zheng, K, Zhang, Y, Bai, F, Mazin, AV, Pei, X-H, Yuan, F & Zhang, Y 2018, 'FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange', Molecular Cell, vol. 71, no. 4, pp. 621-628.e4. https://doi.org/10.1016/j.molcel.2018.06.030
Benitez, Anaid ; Liu, Wenjun ; Palovcak, Anna ; Wang, Guanying ; Moon, Jaewon ; An, Kevin ; Kim, Anna ; Zheng, Kevin ; Zhang, Yu ; Bai, Feng ; Mazin, Alexander V. ; Pei, Xin-Hai ; Yuan, Fenghua ; Zhang, Yanbin. / FANCA Promotes DNA Double-Strand Break Repair by Catalyzing Single-Strand Annealing and Strand Exchange. In: Molecular Cell. 2018 ; Vol. 71, No. 4. pp. 621-628.e4.
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AU - Moon, Jaewon

AU - An, Kevin

AU - Kim, Anna

AU - Zheng, Kevin

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AU - Zhang, Yanbin

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AB - 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. 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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