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This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kuang, Y. Articles by D'Andrea, A. D. Search for Related Content PubMed PubMed Citation Articles by Kuang, Y. Articles by D'Andrea, A. D. Related Collections Plenary Papers Red Cells Social Bookmarking                   What's this? Next Article  Blood, 1 September 2000, Vol. 96, No. 5, pp. 1625-1632 PLENARY PAPER Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity Yanan Kuang, Irene Garcia-Higuera, Anna Moran, Michelle Mondoux, Martin Digweed, and Alan D. D'Andrea From the Department of Pediatric Oncology, Dana-Farber Cancer Institute, and Department of Pediatrics, Children's Hospital, Harvard Medical School, Boston, MA; and Institut fur Humangenetik, Charite-Campus Virchow-Klinikum, Humbodt Universitat Berlin, Germany. Fanconi anemia (FA) is an autosomal recessive cancer susceptibility syndrome with eight complementation groups. Four of the FA genes have been cloned, and at least three of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a nuclear complex, required for the maintenance of normal chromosome stability. In the current study, mutant forms of the FANCA and FANCG proteins have been generated and analyzed with respect to protein complex formation, nuclear translocation, and functional activity. The results demonstrate that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino terminal nuclear localization signal (NLS) of the FANCA protein. On the basis of 2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein interaction. Interestingly, a truncated mutant form of the FANCG protein, lacking the carboxy terminus, binds in a complex with FANCA and translocates to the nucleus; however, this mutant protein fails to bind to FANCC and fails to correct the mitomycin C sensitivity of an FA-G cell line. Taken together, these results demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is necessary but not sufficient for the functional activity of FANCG. Additional amino acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the complex. © 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: J. M. Kim, Y. Kee, A. Gurtan, and A. D. 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Schindler, M. Stumm, M. Grompe, A. Jordan, and K. Sperling Attenuation of the formation of DNA-repair foci containing RAD51 in Fanconi anaemia Carcinogenesis, July 1, 2002; 23(7): 1121 - 1126. [Abstract] [Full Text] [PDF] J. B. Wilson, M. A. Johnson, A. P. Stuckert, K. L. Trueman, S. May, P. E. Bryant, R. E. Meyn, A. D. D'Andrea, and N. J. Jones The Chinese hamster FANCG/XRCC9 mutant NM3 fails to express the monoubiquitinated form of the FANCD2 protein, is hypersensitive to a range of DNA damaging agents and exhibits a normal level of spontaneous sister chromatid exchange Carcinogenesis, December 1, 2001; 22(12): 1939 - 1946. [Abstract] [Full Text] [PDF]

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