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 Westermark, U. K.
Right arrow Articles by Moynahan, M. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Westermark, U. K.
Right arrow Articles by Moynahan, M. E.

 Previous Article

Molecular and Cellular Biology, November 2003, p. 7926-7936, Vol. 23, No. 21
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.21.7926-7936.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

BARD1 Participates with BRCA1 in Homology-Directed Repair of Chromosome Breaks

Ulrica K. Westermark,1 Marsha Reyngold,2 Adam B. Olshen,3 Richard Baer,2 Maria Jasin,1* and Mary Ellen Moynahan4*

Department of Medicine,4 Cell Biology Program,1 Department of Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021,3 Institute for Cancer Genetics, College of Physicians and Surgeons, Columbia University, New York, New York 100322

Received 19 June 2003/ Returned for modification 14 July 2003/ Accepted 24 July 2003

The BRCA1 tumor suppressor has been implicated in the maintenance of chromosomal stability through homology-directed repair of DNA double-strand breaks. Much of the BRCA1 in cells forms a heterodimeric complex with a structurally related protein BARD1. We report that expression of truncated mouse or human BARD1 peptides capable of interacting with Brca1 results in a homologous-repair deficiency. Repair is mildly reduced in Brca1 wild-type cells and severely reduced in cells that harbor a Brca1 splice product deleted for exon 11. Nuclear localization of the Brca1 or BARD1 peptides is not compromised, implying that the repair deficiency is caused by a more direct effect on repair. The tumor suppressor activity of BRCA1 may require the participation of BARD1 to maintain chromosome integrity through the homologous-repair pathway.

* Corresponding authors. Mailing address for Mary Ellen Moynahan: Department of Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Phone: (212) 639-2158. Fax: (212) 717-3317. E-mail: moynaham{at}mskcc.org. Mailing address for Maria Jasin: Cell Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021. Phone: (212) 639-7438. Fax: (212) 717-3317. E-mail: m-jasin{at}ski.mskcc.org.

Molecular and Cellular Biology, November 2003, p. 7926-7936, Vol. 23, No. 21
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.21.7926-7936.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ryser, S., Dizin, E., Jefford, C. E., Delaval, B., Gagos, S., Christodoulidou, A., Krause, K.-H., Birnbaum, D., Irminger-Finger, I. (2009). Distinct Roles of BARD1 Isoforms in Mitosis: Full-Length BARD1 Mediates Aurora B Degradation, Cancer-Associated BARD1{beta} Scaffolds Aurora B and BRCA2. Cancer Res. 69: 1125-1134 [Abstract] [Full Text]  
  • Reid, L. J., Shakya, R., Modi, A. P., Lokshin, M., Cheng, J.-T., Jasin, M., Baer, R., Ludwig, T. (2008). E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks. Proc. Natl. Acad. Sci. USA 105: 20876-20881 [Abstract] [Full Text]  
  • Shakya, R., Szabolcs, M., McCarthy, E., Ospina, E., Basso, K., Nandula, S., Murty, V., Baer, R., Ludwig, T. (2008). The basal-like mammary carcinomas induced by Brca1 or Bard1 inactivation implicate the BRCA1/BARD1 heterodimer in tumor suppression. Proc. Natl. Acad. Sci. USA 105: 7040-7045 [Abstract] [Full Text]  
  • Laufer, M., Nandula, S. V., Modi, A. P., Wang, S., Jasin, M., Murty, V. V. V. S., Ludwig, T., Baer, R. (2007). Structural Requirements for the BARD1 Tumor Suppressor in Chromosomal Stability and Homology-directed DNA Repair. J. Biol. Chem. 282: 34325-34333 [Abstract] [Full Text]  
  • Tembe, V., Henderson, B. R. (2007). BARD1 Translocation to Mitochondria Correlates with Bax Oligomerization, Loss of Mitochondrial Membrane Potential, and Apoptosis. J. Biol. Chem. 282: 20513-20522 [Abstract] [Full Text]  
  • Karppinen, S-M, Barkardottir, R B, Backenhorn, K, Sydenham, T, Syrjakoski, K, Schleutker, J, Ikonen, T, Pylkas, K, Rapakko, K, Erkko, H, Johannesdottir, G, Gerdes, A-M, Thomassen, M, Agnarsson, B A, Grip, M, Kallioniemi, A, Kere, J, Aaltonen, L A, Arason, A, Moller, P, Kruse, T A, Borg, A, Winqvist, R (2006). Nordic collaborative study of the BARD1 Cys557Ser allele in 3956 patients with cancer: enrichment in familial BRCA1/BRCA2 mutation-negative breast cancer but not in other malignancies. J. Med. Genet. 43: 856-862 [Abstract] [Full Text]  
  • Kim, H.-S., Li, H., Cevher, M., Parmelee, A., Fonseca, D., Kleiman, F. E., Lee, S. B. (2006). DNA Damage-Induced BARD1 Phosphorylation Is Critical for the Inhibition of Messenger RNA Processing by BRCA1/BARD1 Complex.. Cancer Res. 66: 4561-4565 [Abstract] [Full Text]  
  • Simons, A. M., Horwitz, A. A., Starita, L. M., Griffin, K., Williams, R. S., Glover, J.N. M., Parvin, J. D. (2006). BRCA1 DNA-Binding Activity Is Stimulated by BARD1. Cancer Res. 66: 2012-2018 [Abstract] [Full Text]  
  • Choudhury, A. D., Xu, H., Modi, A. P., Zhang, W., Ludwig, T., Baer, R. (2005). Hyperphosphorylation of the BARD1 Tumor Suppressor in Mitotic Cells. J. Biol. Chem. 280: 24669-24679 [Abstract] [Full Text]  
  • Schuchner, S., Tembe, V., Rodriguez, J. A., Henderson, B. R. (2005). Nuclear Targeting and Cell Cycle Regulatory Function of Human BARD1. J. Biol. Chem. 280: 8855-8861 [Abstract] [Full Text]  
  • Nakanishi, K., Yang, Y.-G., Pierce, A. J., Taniguchi, T., Digweed, M., D'Andrea, A. D., Wang, Z.-Q., Jasin, M. (2005). Human Fanconi anemia monoubiquitination pathway promotes homologous DNA repair. Proc. Natl. Acad. Sci. USA 102: 1110-1115 [Abstract] [Full Text]  
  • Stark, J. M., Pierce, A. J., Oh, J., Pastink, A., Jasin, M. (2004). Genetic Steps of Mammalian Homologous Repair with Distinct Mutagenic Consequences. Mol. Cell. Biol. 24: 9305-9316 [Abstract] [Full Text]  
  • Karppinen, S-M, Heikkinen, K, Rapakko, K, Winqvist, R (2004). Mutation screening of the BARD1 gene: evidence for involvement of the Cys557Ser allele in hereditary susceptibility to breast cancer. J. Med. Genet. 41: e114-e114 [Full Text]  
  • Choudhury, A. D., Xu, H., Baer, R. (2004). Ubiquitination and Proteasomal Degradation of the BRCA1 Tumor Suppressor Is Regulated during Cell Cycle Progression. J. Biol. Chem. 279: 33909-33918 [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»