Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells

Kazuhiko Yamamoto, Masamichi Ishiai, Nobuko Matsushita, Hiroshi Arakawa, Jane E. Lamerdin, Jean Marie Buerstedde, Mitsune Tanimoto, Mine Harada, Larry H. Thompson, Minoru Takata

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

The rare hereditary disorder Fanconi anemia (FA) is characterized by progressive bone marrow failure, congenital skeletal abnormality, elevated susceptibility to cancer, and cellular hypersensitivity to DNA crosslinking chemicals and sometimes other DNA-damaging agents. Molecular cloning identified six causative genes (FANCA, -C, -D2, -E, -F, and -G) encoding a multiprotein complex whose precise biochemical function remains elusive. Recent studies implicate this complex in DNA damage responses that are linked to the breast cancer susceptibility proteins BRCA1 and BRCA2. Mutations in BRCA2, which participates in homologous recombination (HR), are the underlying cause in some FA patients. To elucidate the roles of FA genes in HR, we disrupted the FANCG/XRCC9 locus in the chicken B-cell line DT40. FANCG-deficient DT40 cells resemble mammalian fancg mutants in that they are sensitive to killing by cisplatin and mitomycin C (MMC) and exhibit increased MMC and radiation-induced chromosome breakage. We find that the repair of I-SceI-induced chromosomal double-strand breaks (DSBs) by HR is decreased ∼9-fold infancg cells compared with the parental and FANCG-complemented cells. In addition, the efficiency of gene targeting is mildly decreased in FANCG-deficient cells, but depends on the specific locus. We conclude that FANCG is required for efficient HR-mediated repair of at least some types of DSBs.

Original languageEnglish
Pages (from-to)5421-5430
Number of pages10
JournalMolecular and Cellular Biology
Volume23
Issue number15
DOIs
Publication statusPublished - Aug 2003

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Fanconi Anemia Complementation Group G Protein
Fanconi Anemia Complementation Group Proteins
Double-Stranded DNA Breaks
Homologous Recombination
Fanconi Anemia
Vertebrates
Radiation
Mitomycin
Enzymes
BRCA2 Protein
BRCA1 Protein
Recombinational DNA Repair
Chromosome Breakage
Multiprotein Complexes
Gene Targeting
DNA
Molecular Cloning
Cisplatin
Genes
DNA Damage

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells. / Yamamoto, Kazuhiko; Ishiai, Masamichi; Matsushita, Nobuko; Arakawa, Hiroshi; Lamerdin, Jane E.; Buerstedde, Jean Marie; Tanimoto, Mitsune; Harada, Mine; Thompson, Larry H.; Takata, Minoru.

In: Molecular and Cellular Biology, Vol. 23, No. 15, 08.2003, p. 5421-5430.

Research output: Contribution to journalArticle

Yamamoto, K, Ishiai, M, Matsushita, N, Arakawa, H, Lamerdin, JE, Buerstedde, JM, Tanimoto, M, Harada, M, Thompson, LH & Takata, M 2003, 'Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells', Molecular and Cellular Biology, vol. 23, no. 15, pp. 5421-5430. https://doi.org/10.1128/MCB.23.15.5421-5430.2003
Yamamoto, Kazuhiko ; Ishiai, Masamichi ; Matsushita, Nobuko ; Arakawa, Hiroshi ; Lamerdin, Jane E. ; Buerstedde, Jean Marie ; Tanimoto, Mitsune ; Harada, Mine ; Thompson, Larry H. ; Takata, Minoru. / Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells. In: Molecular and Cellular Biology. 2003 ; Vol. 23, No. 15. pp. 5421-5430.
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