HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 278, Issue 32, 29487-29495, August 8, 2003

This Article Full Text Full Text (PDF) All Versions of this Article: 278/32/29487    most recent M213251200v1 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Donahue, S. L. Articles by Campbell, C. Search for Related Content PubMed PubMed Citation Articles by Donahue, S. L. Articles by Campbell, C. Social Bookmarking                      What's this?

Deficient Regulation of DNA Double-strand Break Repair in Fanconi Anemia Fibroblasts^*

Sarah L. Donahue, Richard Lundberg, Rachel Saplis and Colin Campbell 

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

Fibroblasts from patients with Fanconi anemia (FA) display genomic instability, hypersensitivity to DNA cross-linking agents, and deficient DNA end joining. Fibroblasts from two FA patients of unidentified complementation group also had significantly increased cellular homologous recombination (HR) activity. Results described herein show that HR activity levels in patient-derived FA fibroblasts of groups A, C, and G were 10-fold greater than those seen in normal fibroblasts. In contrast, HR activity in group D2 fibroblasts was identical to that in normal cells. Western blot analysis revealed that the RAD51 protein was elevated 10-fold above normal levels in group A, C, and G fibroblasts, but was not altered in group D2 fibroblasts. HR activity levels in these former cells could be restored to near-normal levels by electroporation with anti-RAD51 antibody, whereas similar treatment of normal and complementation group D2 fibroblasts had no effect. These findings are consistent with a model in which FA proteins function to coordinate DNA double-strand break repair activity by regulating both recombinational and non-recombinational DNA repair. Interestingly, whereas positive regulation of DNA end joining requires the combined presence of all FA proteins thus far tested, suppression of HR, which is minimally dependent on the FANCA, FANCC, and FANCG proteins, does not require FANCD2.

Received for publication, December 30, 2002 , and in revised form, May 10, 2003.

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

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{at}tc.umn.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				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]

				T. Taniguchi and A. D. D'Andrea Molecular pathogenesis of Fanconi anemia: recent progress Blood, June 1, 2006; 107(11): 4223 - 4233. [Abstract] [Full Text] [PDF]

				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]

				R. D. Kennedy and A. D. D'Andrea The Fanconi Anemia/BRCA pathway: new faces in the crowd Genes & Dev., December 15, 2005; 19(24): 2925 - 2940. [Abstract] [Full Text] [PDF]

				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]

				B. W. Freie, S. L. M. Ciccone, X. Li, P. A. Plett, C. M. Orschell, E. F. Srour, H. Hanenberg, D. Schindler, S.-H. Lee, and D. W. Clapp A Role for the Fanconi Anemia C Protein in Maintaining the DNA Damage-induced G2 Checkpoint J. Biol. Chem., December 3, 2004; 279(49): 50986 - 50993. [Abstract] [Full Text] [PDF]

				S. L. Donahue and C. Campbell A Rad50-dependent pathway of DNA repair is deficient in Fanconi anemia fibroblasts Nucleic Acids Res., June 15, 2004; 32(10): 3248 - 3257. [Abstract] [Full Text] [PDF]