JBC

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1074/jbc.M207937200 on October 1, 2002

J. Biol. Chem., Vol. 277, Issue 48, 46243-46247, November 29, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/48/46243    most recent
M207937200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Donahue, S. L.
Right arrow Articles by Campbell, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Donahue, S. L.
Right arrow Articles by Campbell, C.

A DNA Double Strand Break Repair Defect in Fanconi Anemia Fibroblasts*

Sarah L. Donahue and Colin CampbellDagger

From the Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Fanconi anemia (FA) is a heterogeneous autosomal recessive disease characterized by congenital abnormalities, pancytopenia, and an increased incidence of cancer. Cells cultured from FA patients display elevated spontaneous chromosomal breaks and deletions and are hypersensitive to bifunctional cross-linking agents. Thus, it has been hypothesized that FA is a DNA repair disorder. We analyzed plasmid end-joining in intact diploid fibroblast cells derived from FA patients. FA fibroblasts from complementation groups A, C, D2, and G rejoined linearized plasmids with a significantly decreased efficiency compared with non-FA fibroblasts. Retrovirus-mediated expression of the respective FA cDNAs in FA cells restored their end-joining efficiency to wild type levels. Human FA fibroblasts and fibroblasts from FA rodent models were also significantly more sensitive to restriction enzyme-induced chromosomal DNA double strand breaks than were their retrovirally corrected counterparts. Taken together, these data show that FA fibroblasts have a deficiency in both extra-chromosomal and chromosomal DNA double strand break repair, a defect that could provide an attractive explanation for some of the pathologies associated with FA.

* This work was supported by National Institutes of Health Grant AG16678 and the Breast Cancer Research Program Grant DAMD17-99-1-9299 from the U. S. Department of Defense.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Dept. of Pharmacology, University of Minnesota Medical School, 6-120 Jackson Hall, 321 Church St., S. E., Minneapolis, MN 55455. Tel.: 612-625-8986; Fax: 612-625-8408; E-mail: campb034@tc.umn.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
J. M. Hinz, P. B. Nham, S. S. Urbin, I. M. Jones, and L. H. Thompson
Disparate contributions of the Fanconi anemia pathway and homologous recombination in preventing spontaneous mutagenesis
Nucleic Acids Res., June 28, 2007; 35(11): 3733 - 3740.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Sobeck, S. Stone, and M. E. Hoatlin
DNA Structure-Induced Recruitment and Activation of the Fanconi Anemia Pathway Protein FANCD2
Mol. Cell. Biol., June 15, 2007; 27(12): 4283 - 4292.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
A. Sobeck, S. Stone, V. Costanzo, B. de Graaf, T. Reuter, J. de Winter, M. Wallisch, Y. Akkari, S. Olson, W. Wang, et al.
Fanconi Anemia Proteins Are Required To Prevent Accumulation of Replication-Associated DNA Double-Strand Breaks
Mol. Cell. Biol., January 15, 2006; 26(2): 425 - 437.
[Abstract] [Full Text] [PDF]

Home page
 Hum Mol GenetHome page
S. Houghtaling, A. Newell, Y. Akkari, T. Taniguchi, S. Olson, and M. Grompe
Fancd2 functions in a double strand break repair pathway that is distinct from non-homologous end joining
Hum. Mol. Genet., October 15, 2005; 14(20): 3027 - 3033.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
Y.-G. Yang, Z. Herceg, K. Nakanishi, I. Demuth, C. Piccoli, J. Michelon, G. Hildebrand, M. Jasin, M. Digweed, and Z.-Q. Wang
The Fanconi anemia group A protein modulates homologous repair of DNA double-strand breaks in mammalian cells
Carcinogenesis, October 1, 2005; 26(10): 1731 - 1740.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
W.-H. Park, S. Margossian, A. A. Horwitz, A. M. Simons, A. D. D'Andrea, and J. D. Parvin
Direct DNA Binding Activity of the Fanconi Anemia D2 Protein
J. Biol. Chem., June 24, 2005; 280(25): 23593 - 23598.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. Nakanishi, Y.-G. Yang, A. J. Pierce, T. Taniguchi, M. Digweed, A. D. D'Andrea, Z.-Q. Wang, and M. Jasin
Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair
PNAS, January 25, 2005; 102(4): 1110 - 1115.
[Abstract] [Full Text] [PDF]

Home page
 MutagenesisHome page
J. E. Lamerdin, N. A. Yamada, J. W. George, B. Souza, A. T. Christian, N. J. Jones, and L. H. Thompson
Characterization of the hamster FancG/Xrcc9 gene and mutations in CHO UV40 and NM3
Mutagenesis, May 1, 2004; 19(3): 237 - 244.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
S. L. Donahue, R. Lundberg, R. Saplis, and C. Campbell
Deficient Regulation of DNA Double-strand Break Repair in Fanconi Anemia Fibroblasts
J. Biol. Chem., August 8, 2003; 278(32): 29487 - 29495.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
H. Tonnies, S. Huber, J.-S. Kuhl, A. Gerlach, W. Ebell, and H. Neitzel
Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor
Blood, May 15, 2003; 101(10): 3872 - 3874.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.