This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Näf, D.
Right arrow Articles by D'Andrea, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Näf, D.
Right arrow Articles by D'Andrea, A. D.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, October 1998, p. 5952-5960, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Functional Activity of the Fanconi Anemia Protein FAA Requires FAC Binding and Nuclear Localization

Dieter Näf,1 Gary M. Kupfer,1,2 Ahmed Suliman,1 Kathleen Lambert,1 and Alan D. D'Andrea1,2,*

Division of Pediatric Oncology, Dana-Farber Cancer Institute,1 and Department of Pediatrics, Children's Hospital, Harvard Medical School,2 Boston, Massachusetts

Received 4 March 1998/Returned for modification 15 April 1998/Accepted 19 June 1998

Fanconi anemia (FA) is an autosomal recessive disease characterized by genomic instability, cancer susceptibility, and cellular hypersensitivity to DNA-cross-linking agents. Eight complementation groups of FA (FA-A through FA-H) have been identified. Two FA genes, corresponding to complementation groups FA-A and FA-C, have been cloned, but the functions of the encoded FAA and FAC proteins remain unknown. We have recently demonstrated that FAA and FAC interact to form a nuclear complex. In this study, we have analyzed a series of mutant forms of the FAA protein with respect to functional activity, FAC binding, and nuclear localization. Mutation or deletion of the amino-terminal nuclear localization signal (NLS) of FAA results in loss of functional activity, loss of FAC binding, and cytoplasmic retention of FAA. Replacement of the NLS sequence with a heterologous NLS sequence, derived from the simian virus 40 T antigen, results in nuclear localization but does not rescue functional activity or FAC binding. Nuclear localization of the FAA protein is therefore necessary but not sufficient for FAA function. Mutant forms of FAA which fail to bind to FAC also fail to promote the nuclear accumulation of FAC. In addition, wild-type FAC promotes the accumulation of wild-type FAA in the nucleus. Our results suggest that FAA and FAC perform a concerted function in the cell nucleus, required for the maintenance of chromosomal stability.

* Corresponding author. Mailing address: Division of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02115. Phone: (617) 632-2112. Fax: (617) 632-2085. E-mail: a_dandrea{at}farber.harvard.edu.

Molecular and Cellular Biology, October 1998, p. 5952-5960, Vol. 18, No. 10
0270-7306/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Howlett, N. G., Harney, J. A., Rego, M. A., Kolling, F. W. IV, Glover, T. W. (2009). Functional Interaction between the Fanconi Anemia D2 Protein and Proliferating Cell Nuclear Antigen (PCNA) via a Conserved Putative PCNA Interaction Motif. J. Biol. Chem. 284: 28935-28942 [Abstract] [Full Text]  
  • Collins, N. B., Wilson, J. B., Bush, T., Thomashevski, A., Roberts, K. J., Jones, N. J., Kupfer, G. M. (2009). ATR-dependent phosphorylation of FANCA on serine 1449 after DNA damage is important for FA pathway function. Blood 113: 2181-2190 [Abstract] [Full Text]  
  • Oda, T., Hayano, T., Miyaso, H., Takahashi, N., Yamashita, T. (2007). Hsp90 regulates the Fanconi anemia DNA damage response pathway. Blood 109: 5016-5026 [Abstract] [Full Text]  
  • Kowal, P., Gurtan, A. M., Stuckert, P., D'Andrea, A. D., Ellenberger, T. (2007). Structural Determinants of Human FANCF Protein That Function in the Assembly of a DNA Damage Signaling Complex. J. Biol. Chem. 282: 2047-2055 [Abstract] [Full Text]  
  • Larder, R., Karali, D., Nelson, N., Brown, P. (2006). Fanconi Anemia a Is a Nucleocytoplasmic Shuttling Molecule Required for Gonadotropin-Releasing Hormone (GnRH) Transduction of the GnRH Receptor. Endocrinology 147: 5676-5689 [Abstract] [Full Text]  
  • Pejovic, T., Yates, J. E., Liu, H. Y., Hays, L. E., Akkari, Y., Torimaru, Y., Keeble, W., Rathbun, R. K., Rodgers, W. H., Bale, A. E., Ameziane, N., Zwaan, C. M., Errami, A., Thuillier, P., Cappuccini, F., Olson, S. B., Cain, J. M., Bagby, G. C. Jr. (2006). Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer.. Cancer Res. 66: 9017-9025 [Abstract] [Full Text]  
  • Ho, G. P. H., Margossian, S., Taniguchi, T., D'Andrea, A. D. (2006). Phosphorylation of FANCD2 on Two Novel Sites Is Required for Mitomycin C Resistance.. Mol. Cell. Biol. 26: 7005-7015 [Abstract] [Full Text]  
  • Gurtan, A. M., Stuckert, P., D'Andrea, A. D. (2006). The WD40 Repeats of FANCL Are Required for Fanconi Anemia Core Complex Assembly. J. Biol. Chem. 281: 10896-10905 [Abstract] [Full Text]  
  • Mankad, A., Taniguchi, T., Cox, B., Akkari, Y., Rathbun, R. K., Lucas, L., Bagby, G., Olson, S., D'Andrea, A., Grompe, M. (2006). Natural gene therapy in monozygotic twins with Fanconi anemia. Blood 107: 3084-3090 [Abstract] [Full Text]  
  • Chirnomas, D., Taniguchi, T., de la Vega, M., Vaidya, A. P., Vasserman, M., Hartman, A.-R., Kennedy, R., Foster, R., Mahoney, J., Seiden, M. V., D'Andrea, A. D. (2006). Chemosensitization to cisplatin by inhibitors of the Fanconi anemia/BRCA pathway.. Molecular Cancer Therapeutics 5: 952-961 [Abstract] [Full Text]  
  • Houghtaling, S., Newell, A., Akkari, Y., Taniguchi, T., Olson, S., Grompe, M. (2005). Fancd2 functions in a double strand break repair pathway that is distinct from non-homologous end joining. Hum Mol Genet 14: 3027-3033 [Abstract] [Full Text]  
  • Ferrer, M., Rodriguez, J. A., Spierings, E. A., de Winter, J. P., Giaccone, G., Kruyt, F. A.E. (2005). Identification of multiple nuclear export sequences in Fanconi anemia group A protein that contribute to CRM1-dependent nuclear export. Hum Mol Genet 14: 1271-1281 [Abstract] [Full Text]  
  • Montes de Oca, R., Andreassen, P. R., Margossian, S. P., Gregory, R. C., Taniguchi, T., Wang, X., Houghtaling, S., Grompe, M., D'Andrea, A. D. (2005). Regulated interaction of the Fanconi anemia protein, FANCD2, with chromatin. Blood 105: 1003-1009 [Abstract] [Full Text]  
  • Mi, J., Kupfer, G. M. (2005). The Fanconi anemia core complex associates with chromatin during S phase. Blood 105: 759-766 [Abstract] [Full Text]  
  • Qiao, F., Mi, J., Wilson, J. B., Zhi, G., Bucheimer, N. R., Jones, N. J., Kupfer, G. M. (2004). Phosphorylation of Fanconi Anemia (FA) Complementation Group G Protein, FANCG, at Serine 7 Is Important for Function of the FA Pathway. J. Biol. Chem. 279: 46035-46045 [Abstract] [Full Text]  
  • Mi, J., Qiao, F., Wilson, J. B., High, A. A., Schroeder, M. J., Stukenberg, P. T., Moss, A., Shabanowitz, J., Hunt, D. F., Jones, N. J., Kupfer, G. M. (2004). FANCG Is Phosphorylated at Serines 383 and 387 during Mitosis. Mol. Cell. Biol. 24: 8576-8585 [Abstract] [Full Text]  
  • Van der Heijden, M. S., Brody, J. R., Gallmeier, E., Cunningham, S. C., Dezentje, D. A., Shen, D., Hruban, R. H., Kern, S. E. (2004). Functional Defects in the Fanconi Anemia Pathway in Pancreatic Cancer Cells. Am. J. Pathol. 165: 651-657 [Abstract] [Full Text]  
  • Park, S.-J., Ciccone, S. L. M., Beck, B. D., Hwang, B., Freie, B., Clapp, D. W., Lee, S.-H. (2004). Oxidative Stress/Damage Induces Multimerization and Interaction of Fanconi Anemia Proteins. J. Biol. Chem. 279: 30053-30059 [Abstract] [Full Text]  
  • Thomashevski, A., High, A. A., Drozd, M., Shabanowitz, J., Hunt, D. F., Grant, P. A., Kupfer, G. M. (2004). The Fanconi Anemia Core Complex Forms Four Complexes of Different Sizes in Different Subcellular Compartments. J. Biol. Chem. 279: 26201-26209 [Abstract] [Full Text]  
  • Lensch, M. W., Tischkowitz, M., Christianson, T. A., Reifsteck, C. A., Speckhart, S. A., Jakobs, P. M., O'Dwyer, M. E., Olson, S. B., Le Beau, M. M., Hodgson, S. V., Mathew, C. G., Larson, R. A., Bagby, G. C. Jr (2003). Acquired FANCA dysfunction and cytogenetic instability in adult acute myelogenous leukemia. Blood 102: 7-16 [Abstract] [Full Text]  
  • Gordon, S. M., Buchwald, M. (2003). Fanconi anemia protein complex: mapping protein interactions in the yeast 2- and 3-hybrid systems. Blood 102: 136-141 [Abstract] [Full Text]  
  • Shimamura, A., de Oca, R. M., Svenson, J. L., Haining, N., Moreau, L. A., Nathan, D. G., D'Andrea, A. D. (2002). A novel diagnostic screen for defects in the Fanconi anemia pathway. Blood 100: 4649-4654 [Abstract] [Full Text]  
  • Pang, Q., Christianson, T. A., Keeble, W., Koretsky, T., Bagby, G. C. (2002). The Anti-apoptotic Function of Hsp70 in the Interferon-inducible Double-stranded RNA-dependent Protein Kinase-mediated Death Signaling Pathway Requires the Fanconi Anemia Protein, FANCC. J. Biol. Chem. 277: 49638-49643 [Abstract] [Full Text]  
  • Adachi, D., Oda, T., Yagasaki, H., Nakasato, K., Taniguchi, T., D'Andrea, A. D., Asano, S., Yamashita, T. (2002). Heterogeneous activation of the Fanconi anemia pathway by patient-derived FANCA mutants. Hum Mol Genet 11: 3125-3134 [Abstract] [Full Text]  
  • Folias, A., Matkovic, M., Bruun, D., Reid, S., Hejna, J., Grompe, M., D'Andrea, A., Moses, R. (2002). BRCA1 interacts directly with the Fanconi anemia protein FANCA. Hum Mol Genet 11: 2591-2597 [Abstract] [Full Text]  
  • Taniguchi, T., Garcia-Higuera, I., Andreassen, P. R., Gregory, R. C., Grompe, M., D'Andrea, A. D. (2002). S-phase-specific interaction of the Fanconi anemia protein, FANCD2, with BRCA1 and RAD51. Blood 100: 2414-2420 [Abstract] [Full Text]  
  • Taniguchi, T., D'Andrea, A. D. (2002). The Fanconi anemia protein, FANCE, promotes the nuclear accumulation of FANCC. Blood 100: 2457-2462 [Abstract] [Full Text]  
  • Yagasaki, H., Adachi, D., Oda, T., Garcia-Higuera, I., Tetteh, N., D'Andrea, A. D., Futaki, M., Asano, S., Yamashita, T. (2001). A cytoplasmic serine protein kinase binds and may regulate the Fanconi anemia protein FANCA. Blood 98: 3650-3657 [Abstract] [Full Text]  
  • Li, B., Zhang, W., Chan, G., Jancso-Radek, A., Liu, S., Weiss, M. A. (2001). Human Sex Reversal Due to Impaired Nuclear Localization of SRY. A CLINICAL CORRELATION. J. Biol. Chem. 276: 46480-46484 [Abstract] [Full Text]  
  • Pang, Q., Christianson, T. A., Keeble, W., Diaz, J., Faulkner, G. R., Reifsteck, C., Olson, S., Bagby, G. C. (2001). The Fanconi anemia complementation group C gene product: structural evidence of multifunctionality. Blood 98: 1392-1401 [Abstract] [Full Text]  
  • Santagati, F., Botta, E., Stefanini, M., Pedrini, A. M. (2001). Different dynamics in nuclear entry of subunits of the repair/transcription factor TFIIH. Nucleic Acids Res 29: 1574-1581 [Abstract] [Full Text]  
  • Medhurst, A. L., Huber, P. A.J., Waisfisz, Q., de Winter, J. P., Mathew, C. G. (2001). Direct interactions of the five known Fanconi anaemia proteins suggest a common functional pathway. Hum Mol Genet 10: 423-429 [Abstract] [Full Text]  
  • de Winter, J. P., van der Weel, L., de Groot, J., Stone, S., Waisfisz, Q., Arwert, F., Scheper, R. J., Kruyt, F. A.E., Hoatlin, M. E., Joenje, H. (2000). The Fanconi anemia protein FANCF forms a nuclear complex with FANCA, FANCC and FANCG. Hum Mol Genet 9: 2665-2674 [Abstract] [Full Text]  
  • Garcia-Higuera, I., Kuang, Y., Denham, J., D'Andrea, A. D. (2000). The Fanconi anemia proteins FANCA and FANCG stabilize each other and promote the nuclear accumulation of the Fanconi anemia complex. Blood 96: 3224-3230 [Abstract] [Full Text]  
  • Kuang, Y., Garcia-Higuera, I., Moran, A., Mondoux, M., Digweed, M., D'Andrea, A. D. (2000). Carboxy terminal region of the Fanconi anemia protein, FANCG/XRCC9, is required for functional activity. Blood 96: 1625-1632 [Abstract] [Full Text]  
  • Heinrich, M. C., Silvey, K. V., Stone, S., Zigler, A. J., Griffith, D. J., Montalto, M., Chai, L., Zhi, Y., Hoatlin, M. E. (2000). Posttranscriptional cell cycle-dependent regulation of human FANCC expression. Blood 95: 3970-3977 [Abstract] [Full Text]  
  • Reuter, T., Herterich, S., Bernhard, O., Hoehn, H., Gross, H. J. (2000). Strong FANCA/FANCG but weak FANCA/FANCC interaction in the yeast 2-hybrid system. Blood 95: 719-720 [Abstract] [Full Text]  
  • Pasion, S. G., Forsburg, S. L. (1999). Nuclear Localization of Schizosaccharomyces pombe Mcm2/Cdc19p Requires MCM Complex Assembly. Mol. Biol. Cell 10: 4043-4057 [Abstract] [Full Text]  
  • Hoatlin, M. E., Zhi, Y., Ball, H., Silvey, K., Melnick, A., Stone, S., Arai, S., Hawe, N., Owen, G., Zelent, A., Licht, J. D. (1999). A Novel BTB/POZ Transcriptional Repressor Protein Interacts With the Fanconi Anemia Group C Protein and PLZF. Blood 94: 3737-3747 [Abstract] [Full Text]  
  • Kruyt, F. A. E., Abou-Zahr, F., Mok, H., Youssoufian, H. (1999). Resistance to Mitomycin C Requires Direct Interaction between the Fanconi Anemia Proteins FANCA and FANCG in the Nucleus through an Arginine-rich Domain. J. Biol. Chem. 274: 34212-34218 [Abstract] [Full Text]  
  • Brois, D. W., McMahon, L. W., Ramos, N. I., Anglin, L. M., Walsh, C. E., Lambert, M. W. (1999). A deficiency in a 230 kDa DNA repair protein in Fanconi anemia complementation group A cells is corrected by the FANCA cDNA. Carcinogenesis 20: 1845-1853 [Abstract] [Full Text]  
  • Waisfisz, Q., de Winter, J. P., Kruyt, F. A. E., de Groot, J., van der Weel, L., Dijkmans, L. M., Zhi, Y., Arwert, F., Scheper, R. J., Youssoufian, H., Hoatlin, M. E., Joenje, H. (1999). A physical complex of the Fanconi anemia proteins FANCG/XRCC9 and FANCA. Proc. Natl. Acad. Sci. USA 96: 10320-10325 [Abstract] [Full Text]  
  • Abu-Issa, R., Eichele, G., Youssoufian, H. (1999). Expression of the Fanconi Anemia Group A Gene (Fanca) During Mouse Embryogenesis. Blood 94: 818-824 [Abstract] [Full Text]  
  • Garcia-Higuera, I., Kuang, Y., Naf, D., Wasik, J., D'Andrea, A. D. (1999). Fanconi Anemia Proteins FANCA, FANCC, and FANCG/XRCC9 Interact in a Functional Nuclear Complex. Mol. Cell. Biol. 19: 4866-4873 [Abstract] [Full Text]  
  • Savoia, A., Garcia-Higuera, I., D'Andrea, A. D. (1999). Nuclear Localization of the Fanconi Anemia Protein FANCC Is Required for Functional Activity. Blood 93: 4025-4026 [Full Text]  
  • Garcia-Higuera, I., D'Andrea;, A. D., Kruyt, F. A.E., Youssoufian, H. (1999). Regulated Binding of the Fanconi Anemia Proteins, FANCA and FANCC. Blood 93: 1430-1432 [Full Text]  
  • Yamashita, T., Kupfer, G. M., Naf, D., Suliman, A., Joenje, H., Asano, S., D'Andrea, A. D. (1998). The Fanconi anemia pathway requires FAA phosphorylation and FAA/FAC nuclear accumulation. Proc. Natl. Acad. Sci. USA 95: 13085-13090 [Abstract] [Full Text]  
  • Qiao, F., Moss, A., Kupfer, G. M. (2001). Fanconi Anemia Proteins Localize to Chromatin and the Nuclear Matrix in a DNA Damage- and Cell Cycle-regulated Manner. J. Biol. Chem. 276: 23391-23396 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»