Characterization of the hamster FancG/Xrcc9 gene and mutations in CHO UV40 and NM3

Jane E. Lamerdin, Nazumi A. Yamada, James W. George, Brian Souza, Allen T. Christian, Nigel J. Jones, Larry H. Thompson

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

The human FANCG/XRCC9 gene, which is defective in Fanconi anemia complementation group G (FA-G) cells, was first cloned by genetic complementation of the mitomycin C (MMC) sensitivity of CHO mutant UV40. The CHO NM3 mutant was subsequently assigned to the same complementation group. The parental AA8 CHO cells are hemizygous at the FancG locus, and we identified frame-shift mutations that result in N-terminal truncations of the protein in both UV40 and NM3. Hypersensitivity to DNA cross-linking agents, such as MMC, typically characterizes FA cells. By introducing the native CHO FancG gene into mutant NM3, we demonstrate that hamster FancG fully corrects the 3-fold sensitivity to methyl methanesulfonate (MMS) as well as the 10-fold sensitivity to MMC, whereas resistance to ionizing radiation did not increase appreciably. In contrast, hamster cDNA transformants showed incomplete correction for both MMC and MMS sensitivity. The constitutively expressed FancG protein is present in the cytoplasmic, nuclear and chromatin fractions. FancG protein levels and subcellular localization do not change appreciably as a function of cell cycle position. Our results are consistent with roles of FancG in both the nuclear and cytoplasmic compartments to maintain genomic stability in response to various genotoxic agents.

Original languageEnglish (US)
Pages (from-to)237-244
Number of pages8
JournalMutagenesis
Volume19
Issue number3
DOIs
StatePublished - May 2004
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

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    Lamerdin, J. E., Yamada, N. A., George, J. W., Souza, B., Christian, A. T., Jones, N. J., & Thompson, L. H. (2004). Characterization of the hamster FancG/Xrcc9 gene and mutations in CHO UV40 and NM3. Mutagenesis, 19(3), 237-244. https://doi.org/10.1093/mutage/geh019