Fanconi anemia proteins localize to chromatin and the nuclear matrix in a DNA damage- and cell cycle-regulated manner.
Fanconi anemia (FA) is a genetic disease characterized by congenital defects, bone marrow failure, and cancer susceptibility. Cells from patients with FA exhibit genomic instability and hypersensitivity to DNA cross linking agents such as mitomycin C. Despite the identification of seven complementation groups and the cloning of six genes, the ... function of the encoded gene products remains elusive. The FancA (Fanconi anemia complementation group A), FancC, and FancG proteins have been detected within a nuclear complex, but no change in level, binding, or localization has been reported as a result of drug treatment or cell cycle. We show that in immunofluorescence studies, FancA appears as a non-nucleolar nuclear protein that is excluded from condensed, mitotic chromosomes. Biochemical fractionation reveals that the FA proteins are found in nuclear matrix and chromatin and that treatment with mitomycin C results in increase of the FA proteins in nuclear matrix and chromatin fractions. This induction occurs in wild-type cells and mutant FA-D (Fanconi complementation group D) cells but not in mutant FA-A cells. Immunoprecipitation of FancA protein in chromatin demonstrates the coprecipitation of FancA, FancC, and FancG, showing that the FA proteins move together as a complex. Also, fractionation of mitotic cells confirms the lack of FA proteins in chromatin or the nuclear matrix. Furthermore, phosphorylation of FancG was found to be temporally correlated with exit of the FA complex from chromosomes at mitosis. Taken together, these findings suggest a role for FA proteins in chromatin and nuclear matrix.
Mesh Terms:
Cell Cycle, Cell Cycle Proteins, Cell Nucleolus, Chromatin, Chromosomes, DNA Damage, DNA-Binding Proteins, Deoxyribonucleases, Fanconi Anemia, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group G Protein, Fanconi Anemia Complementation Group Proteins, Hela Cells, Humans, Mitomycin, Mitosis, Nuclear Matrix, Nuclear Proteins, Phosphorylation, Precipitin Tests, Proteins
Cell Cycle, Cell Cycle Proteins, Cell Nucleolus, Chromatin, Chromosomes, DNA Damage, DNA-Binding Proteins, Deoxyribonucleases, Fanconi Anemia, Fanconi Anemia Complementation Group A Protein, Fanconi Anemia Complementation Group C Protein, Fanconi Anemia Complementation Group G Protein, Fanconi Anemia Complementation Group Proteins, Hela Cells, Humans, Mitomycin, Mitosis, Nuclear Matrix, Nuclear Proteins, Phosphorylation, Precipitin Tests, Proteins
J. Biol. Chem.
Date: Jun. 29, 2001
PubMed ID: 11297559
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