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 Arlt, M. F.
Right arrow Articles by Glover, T. W.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arlt, M. F.
Right arrow Articles by Glover, T. W.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, August 2004, p. 6701-6709, Vol. 24, No. 15
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.15.6701-6709.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

BRCA1 Is Required for Common-Fragile-Site Stability via Its G2/M Checkpoint Function

Martin F. Arlt,1 Bo Xu,2 Sandra G. Durkin,1 Anne M. Casper,1 Michael B. Kastan,3 and Thomas W. Glover1*

Department of Human Genetics, University of Michigan, Ann Arbor, Michigan 48109,1 Department of Genetics and Stanley S. Scott Cancer Center, Louisiana State University Health Science Center, New Orleans, Louisiana 70112,2 Department of Hematology-Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee 381053

Received 9 January 2004/ Returned for modification 4 March 2004/ Accepted 4 May 2004

Common fragile sites are loci that form chromosome gaps or breaks when DNA synthesis is partially inhibited. Fragile sites are prone to deletions, translocations, and other rearrangements that can cause the inactivation of associated tumor suppressor genes in cancer cells. It was previously shown that ATR is critical to fragile-site stability and that ATR-deficient cells have greatly elevated fragile-site expression (A. M. Casper, P. Nghiem, M. F. Arlt, and T. W. Glover, Cell 111:779-789, 2002). Here we demonstrate that mouse and human cells deficient for BRCA1, due to mutation or knockdown by RNA interference, also have elevated fragile-site expression. We further show that BRCA1 functions in the induction of the G2/M checkpoint after aphidicolin-induced replication stalling and that this checkpoint function is involved in fragile-site stability. These data indicate that BRCA1 is important in fragile-site stability and that fragile sites are recognized by the G2/M checkpoint pathway, in which BRCA1 plays a key role. Furthermore, they suggest that mutations in BRCA1 or interacting proteins could lead to rearrangements at fragile sites in cancer cells.

* Corresponding author. Mailing address: Department of Human Genetics, 4909 Buhl, Box 0618, 1241 E. Catherine St., University of Michigan, Ann Arbor, MI 48109-0618. Phone: (734) 763-5222. Fax: (734) 763-3784. E-mail: glover{at}umich.edu.

Molecular and Cellular Biology, August 2004, p. 6701-6709, Vol. 24, No. 15
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.15.6701-6709.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kumari, D., Somma, V., Nakamura, A. J., Bonner, W. M., D'Ambrosio, E., Usdin, K. (2009). The role of DNA damage response pathways in chromosome fragility in Fragile X syndrome. Nucleic Acids Res 37: 4385-4392 [Abstract] [Full Text]  
  • Richard, G.-F., Kerrest, A., Dujon, B. (2008). Comparative Genomics and Molecular Dynamics of DNA Repeats in Eukaryotes. Microbiol. Mol. Biol. Rev. 72: 686-727 [Abstract] [Full Text]  
  • Usdin, K. (2008). The biological effects of simple tandem repeats: Lessons from the repeat expansion diseases. Genome Res 18: 1011-1019 [Abstract] [Full Text]  
  • Ishii, H., Mimori, K., Ishikawa, K., Okumura, H., Pichiorri, F., Druck, T., Inoue, H., Vecchione, A., Saito, T., Mori, M., Huebner, K. (2008). Fhit-Deficient Hematopoietic Stem Cells Survive Hydroquinone Exposure Carrying Precancerous Changes. Cancer Res. 68: 3662-3670 [Abstract] [Full Text]  
  • Pirzio, L. M., Pichierri, P., Bignami, M., Franchitto, A. (2008). Werner syndrome helicase activity is essential in maintaining fragile site stability. JCB 180: 305-314 [Abstract] [Full Text]  
  • Durkin, S. G., Ragland, R. L., Arlt, M. F., Mulle, J. G., Warren, S. T., Glover, T. W. (2008). Replication stress induces tumor-like microdeletions in FHIT/FRA3B. Proc. Natl. Acad. Sci. USA 105: 246-251 [Abstract] [Full Text]  
  • Debacker, K., Winnepenninckx, B., Ben-Porat, N., FitzPatrick, D., Van Luijk, R., Scheers, S., Kerem, B., Frank Kooy, R (2007). FRA18C: a new aphidicolin-inducible fragile site on chromosome 18q22, possibly associated with in vivo chromosome breakage. J. Med. Genet. 44: 347-352 [Abstract] [Full Text]  
  • Koren, A. (2007). The role of the DNA damage checkpoint in regulation of translesion DNA synthesis. Mutagenesis 22: 155-160 [Abstract] [Full Text]  
  • Zhu, M., Weiss, R. S. (2007). Increased Common Fragile Site Expression, Cell Proliferation Defects, and Apoptosis following Conditional Inactivation of Mouse Hus1 in Primary Cultured Cells. Mol. Biol. Cell 18: 1044-1055 [Abstract] [Full Text]  
  • Ishii, H., Mimori, K., Inoue, H., Inageta, T., Ishikawa, K., Semba, S., Druck, T., Trapasso, F., Tani, K., Vecchione, A., Croce, C. M., Mori, M., Huebner, K. (2006). Fhit Modulates the DNA Damage Checkpoint Response. Cancer Res. 66: 11287-11292 [Abstract] [Full Text]  
  • Diaz-Perez, S. V., Ferguson, D. O., Wang, C., Csankovszki, G., Wang, C., Tsai, S.-C., Dutta, D., Perez, V., Kim, S., Eller, C. D., Salstrom, J., Ouyang, Y., Teitell, M. A., Kaltenboeck, B., Chess, A., Huang, S., Marahrens, Y. (2006). A Deletion at the Mouse Xist Gene Exposes Trans-effects That Alter the Heterochromatin of the Inactive X Chromosome and the Replication Time and DNA Stability of Both X Chromosomes. Genetics 174: 1115-1133 [Abstract] [Full Text]  
  • Helmrich, A., Stout-Weider, K., Hermann, K., Schrock, E., Heiden, T. (2006). Common fragile sites are conserved features of human and mouse chromosomes and relate to large active genes. Genome Res 16: 1222-1230 [Abstract] [Full Text]  
  • Admire, A., Shanks, L., Danzl, N., Wang, M., Weier, U., Stevens, W., Hunt, E., Weinert, T. (2006). Cycles of chromosome instability are associated with a fragile site and are increased by defects in DNA replication and checkpoint controls in yeast. Genes Dev. 20: 159-173 [Abstract] [Full Text]  
  • Kim, J.-E., McAvoy, S. A., Smith, D. I., Chen, J. (2005). Human TopBP1 Ensures Genome Integrity during Normal S Phase. Mol. Cell. Biol. 25: 10907-10915 [Abstract] [Full Text]  
  • El Achkar, E., Gerbault-Seureau, M., Muleris, M., Dutrillaux, B., Debatisse, M. (2005). Premature condensation induces breaks at the interface of early and late replicating chromosome bands bearing common fragile sites. Proc. Natl. Acad. Sci. USA 102: 18069-18074 [Abstract] [Full Text]  
  • Schwartz, M., Zlotorynski, E., Goldberg, M., Ozeri, E., Rahat, A., Sage, C. l., Chen, B. P.C., Chen, D. J., Agami, R., Kerem, B. (2005). Homologous recombination and nonhomologous end-joining repair pathways regulate fragile site stability. Genes Dev. 19: 2715-2726 [Abstract] [Full Text]  
  • Glover, T. W., Arlt, M. F., Casper, A. M., Durkin, S. G. (2005). Mechanisms of common fragile site instability. Hum Mol Genet 14: R197-R205 [Abstract] [Full Text]  
  • Finnis, M., Dayan, S., Hobson, L., Chenevix-Trench, G., Friend, K., Ried, K., Venter, D., Woollatt, E., Baker, E., Richards, R. I. (2005). Common chromosomal fragile site FRA16D mutation in cancer cells. Hum Mol Genet 14: 1341-1349 [Abstract] [Full Text]  
  • Howlett, N. G., Taniguchi, T., Durkin, S. G., D'Andrea, A. D., Glover, T. W. (2005). The Fanconi anemia pathway is required for the DNA replication stress response and for the regulation of common fragile site stability. Hum Mol Genet 14: 693-701 [Abstract] [Full Text]  
  • Musio, A., Montagna, C., Mariani, T., Tilenni, M., Focarelli, M. L., Brait, L., Indino, E., Benedetti, P. A., Chessa, L., Albertini, A., Ried, T., Vezzoni, P. (2005). SMC1 involvement in fragile site expression. Hum Mol Genet 14: 525-533 [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»