Oxidative stress/damage induces multimerization and interaction of fanconi anemia proteins

Su Jung Park, Samantha L M Ciccone, Brian D. Beck, Byounghoon Hwang, Brian Freie, D. Clapp, Suk-Hee Lee

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Fanconi anemia (FANC) is a heterogeneous genetic disorder characterized by a hypersensitivity to DNA-damaging agents, chromosomal instability, and defective DNA repair. Eight FANC genes have been identified so far, and five of them (FANCA, -C, -E, -F, and -G) assemble in a multinuclear complex and function at least in part in a complex to activate FANCD2 by monoubiquitination. Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized and/or form a nuclear complex in response to oxidative stress/damage. Both FANCA and FANCG proteins exist as monomers under non-oxidizing conditions, whereas they become multimers following H2O2 treatment. Treatment of cells with oxidizing agent not only triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between FANCA and FANCG. N-Ethylmaleimide treatment abolishes multimerization and interaction of FANCA and FANCG in vitro. Taken together, our results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming complex(es) via intermolecular disulfide linkage(s), which may be crucial in forming such complexes and in determining their function.

Original languageEnglish
Pages (from-to)30053-30059
Number of pages7
JournalJournal of Biological Chemistry
Volume279
Issue number29
DOIs
StatePublished - Jul 16 2004

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Fanconi Anemia Complementation Group Proteins
Fanconi Anemia
Oxidative stress
Fanconi Anemia Complementation Group G Protein
Fanconi Anemia Complementation Group A Protein
Oxidative Stress
Chromosomal Instability
Inborn Genetic Diseases
Ethylmaleimide
DNA
Oxidants
DNA Repair
Disulfides
Oxidation-Reduction
Hypersensitivity
Repair
Genes
Monomers
Cells
Proteins

ASJC Scopus subject areas

  • Biochemistry

Cite this

Oxidative stress/damage induces multimerization and interaction of fanconi anemia proteins. / Park, Su Jung; Ciccone, Samantha L M; Beck, Brian D.; Hwang, Byounghoon; Freie, Brian; Clapp, D.; Lee, Suk-Hee.

In: Journal of Biological Chemistry, Vol. 279, No. 29, 16.07.2004, p. 30053-30059.

Research output: Contribution to journalArticle

Park, Su Jung ; Ciccone, Samantha L M ; Beck, Brian D. ; Hwang, Byounghoon ; Freie, Brian ; Clapp, D. ; Lee, Suk-Hee. / Oxidative stress/damage induces multimerization and interaction of fanconi anemia proteins. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 29. pp. 30053-30059.
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