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Gene Review:

Fancg - Fanconi anemia, complementation group G

Mus musculus

Synonyms: AU041407, Fanconi anemia group G protein homolog, Protein FACG, Xrcc9

Koomen, M. et al., Yang, Y. et al., Yamamoto, K. et al., van de Vrugt, H.J. et al., Si, Y. et al., et al.

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Disease relevance of Fancg

Male and female mice deficient in Fancg showed hypogonadism and impaired fertility, consistent with the phenotype of FA patients [1].
Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9 [2].
Expression of mouse Fancg in human FA-G lymphoblasts fully corrects their cross-linker hypersensitivity [3].
Here we report inherited and somatic mutations of FANCC and FANCG present in young-onset pancreatic cancer [4].

High impact information on Fancg

Continuous in vivo infusion of interferon-gamma (IFN-{gamma}) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice [5].
Telomere dynamics in Fancg-deficient mouse and human cells [6].
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 [7].
Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells [7].
During a 1 year follow-up, blood cell parameters of Fancg KO mice remained within normal values, revealing no signs of anemia [1].

Biological context of Fancg

Primary splenic lymphocytes, bone marrow progenitor cells, and murine embryo fibroblasts from the Fancg(-/-) mice demonstrated spontaneous chromosome breakage and increased sensitivity to mitomycin C and, to a lesser extent, ionizing radiation [2].
Finally, Fancg(-/-) mice had decreased fertility and abnormal gonadal histology [2].
The mouse Fancg sequence was established in order to evaluate missense mutations [8].
Upon transfection into Fanca-deficient mouse embryonic fibroblasts EGFP-Fancg chimeric protein was detectable in the nucleus [3].

Anatomical context of Fancg

The sensitivity to UV, X-rays and methyl methanesulfonate, reported for the CHO mutant cell line UV40, was not observed in Fancg(-/-) MEFs [1].
Spleen, thymus and testis showed the highest Fancg expression levels [3].

Analytical, diagnostic and therapeutic context of Fancg

The Fancg(-/-) mouse may be useful as an animal model for future gene therapy and cancer susceptibility studies [2].
In addition, mouse Fancg and Fanca proteins co-purify by immunoprecipitation [3].
In addition, the efficiency of gene targeting is mildly decreased in FANCG-deficient cells, but depends on the specific locus [7].

References

Reduced fertility and hypersensitivity to mitomycin C characterize Fancg/Xrcc9 null mice. Koomen, M., Cheng, N.C., van de Vrugt, H.J., Godthelp, B.C., van der Valk, M.A., Oostra, A.B., Zdzienicka, M.Z., Joenje, H., Arwert, F. Hum. Mol. Genet. (2002) [Pubmed]
Targeted disruption of the murine Fanconi anemia gene, Fancg/Xrcc9. Yang, Y., Kuang, Y., De Oca, R.M., Hays, T., Moreau, L., Lu, N., Seed, B., D'Andrea, A.D. Blood (2001) [Pubmed]
Characterization, expression and complex formation of the murine Fanconi anaemia gene product Fancg. van de Vrugt, H.J., Koomen, M., Berns, M.A., de Vries, Y., Rooimans, M.A., van der Weel, L., Blom, E., de Groot, J., Schepers, R.J., Stone, S., Hoatlin, M.E., Cheng, N.C., Joenje, H., Arwert, F. Genes Cells (2002) [Pubmed]
Fanconi anemia gene mutations in young-onset pancreatic cancer. van der Heijden, M.S., Yeo, C.J., Hruban, R.H., Kern, S.E. Cancer Res. (2003) [Pubmed]
Continuous in vivo infusion of interferon-gamma (IFN-{gamma}) enhances engraftment of syngeneic wild-type cells in Fanca-/- and Fancg-/- mice. Si, Y., Ciccone, S., Yang, F.C., Yuan, J., Zeng, D., Chen, S., van de Vrugt, H.J., Critser, J., Arwert, F., Haneline, L.S., Clapp, D.W. Blood (2006) [Pubmed]
Telomere dynamics in Fancg-deficient mouse and human cells. Franco, S., van de Vrugt, H.J., Fernández, P., Aracil, M., Arwert, F., Blasco, M.A. Blood (2004) [Pubmed]
Fanconi anemia FANCG protein in mitigating radiation- and enzyme-induced DNA double-strand breaks by homologous recombination in vertebrate cells. Yamamoto, K., Ishiai, M., Matsushita, N., Arakawa, H., Lamerdin, J.E., Buerstedde, J.M., Tanimoto, M., Harada, M., Thompson, L.H., Takata, M. Mol. Cell. Biol. (2003) [Pubmed]
Spectrum of mutations in the Fanconi anaemia group G gene, FANCG/XRCC9. Demuth, I., Wlodarski, M., Tipping, A.J., Morgan, N.V., de Winter, J.P., Thiel, M., Gräsl, S., Schindler, D., D'Andrea, A.D., Altay, C., Kayserili, H., Zatterale, A., Kunze, J., Ebell, W., Mathew, C.G., Joenje, H., Sperling, K., Digweed, M. Eur. J. Hum. Genet. (2000) [Pubmed]

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