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Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 November 2000, Vol. 96, No. 9, pp. 3224-3230 RED CELLS The Fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex Irene Garcia-Higuera, Yanan Kuang, Jessica Denham, and Alan D. D'Andrea From the Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA. Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with 8 complementation groups. Four of the FA genes have been cloned, and at least 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex. The FANCG protein binds directly to the amino terminal nuclear localization sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulation. In the current study the functional consequences of FANCG/FANCA binding were examined. Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of FANCA, and an increase in the nuclear accumulation of the FA protein complex. Similar results were obtained upon correction of an FA-A cell line, with a reciprocal increase in the half-life of FANCG. Patient-derived mutant forms of FANCA, containing an intact NLS sequence but point mutations in the carboxy-terminal leucine zipper region, bound FANCG in the cytoplasm. The mutant forms failed to translocate to the nucleus of transduced cells, thereby suggesting a model of coordinated binding and nuclear translocation. These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular levels of both proteins. Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation of the FA protein complex. Failure to accumulate the nuclear FA protein complex results in the characteristic spectrum of clinical and cellular abnormalities observed in FA. © 2000 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Yuan, J. El Hokayem, W. Zhou, and Y. Zhang FANCI Protein Binds to DNA and Interacts with FANCD2 to Recognize Branched Structures J. Biol. Chem., September 4, 2009; 284(36): 24443 - 24452. [Abstract] [Full Text] [PDF] C. S. Tremblay, C. C. Huard, F.-F. Huang, O. Habi, V. Bourdages, G. Levesque, and M. Carreau The Fanconi Anemia Core Complex Acts as a Transcriptional Co-regulator in Hairy Enhancer of Split 1 Signaling J. Biol. Chem., May 15, 2009; 284(20): 13384 - 13395. [Abstract] [Full Text] [PDF] Y. Kee, J. M. Kim, and A. D'Andrea Regulated degradation of FANCM in the Fanconi anemia pathway during mitosis Genes & Dev., March 1, 2009; 23(5): 555 - 560. 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