This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental material
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 E-mail 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 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 Wei, L.
Right arrow Articles by Chiba, N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wei, L.
Right arrow Articles by Chiba, N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, December 2008, p. 7380-7393, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.01075-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Rapid Recruitment of BRCA1 to DNA Double-Strand Breaks Is Dependent on Its Association with Ku80{triangledown} ,{dagger}

Leizhen Wei,1 Li Lan,2 Zehui Hong,2 Akira Yasui,2 Chikashi Ishioka,1 and Natsuko Chiba1*

Department of Clinical Oncology,1 Department of Molecular Genetics, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan2

Received 9 July 2008/ Returned for modification 29 August 2008/ Accepted 7 October 2008

BRCA1 is the first susceptibility gene to be linked to breast and ovarian cancers. Although mounting evidence has indicated that BRCA1 participates in DNA double-strand break (DSB) repair pathways, its precise mechanism is still unclear. Here, we analyzed the in situ response of BRCA1 at DSBs produced by laser microirradiation. The amino (N)- and carboxyl (C)-terminal fragments of BRCA1 accumulated independently at DSBs with distinct kinetics. The N-terminal BRCA1 fragment accumulated immediately after laser irradiation at DSBs and dissociated rapidly. In contrast, the C-terminal fragment of BRCA1 accumulated more slowly at DSBs but remained at the sites. Interestingly, rapid accumulation of the BRCA1 N terminus, but not the C terminus, at DSBs depended on Ku80, which functions in the nonhomologous end-joining (NHEJ) pathway, independently of BARD1, which binds to the N terminus of BRCA1. Two small regions in the N terminus of BRCA1 independently accumulated at DSBs and interacted with Ku80. Missense mutations found within the N terminus of BRCA1 in cancers significantly changed the kinetics of its accumulation at DSBs. A P142H mutant failed to associate with Ku80 and restore resistance to irradiation in BRCA1-deficient cells. These might provide a molecular basis of the involvement of BRCA1 in the NHEJ pathway of the DSB repair process.

* Corresponding author. Present address: Department of Molecular Immunology, Institute of Development, Aging and Cancer (IDAC), Tohoku University, 4-1 Seiryomachi Aoba-ku, Sendai 980-8575, Japan. Phone: 81-22-717-8478. Fax: 81-22-717-8482. E-mail: nchiba{at}idac.tohoku.ac.jp

{triangledown} Published ahead of print on 20 October 2008.

{dagger} Supplemental material for this paper may be found at http://mcb.asm.org/.

Molecular and Cellular Biology, December 2008, p. 7380-7393, Vol. 28, No. 24
0270-7306/08/$08.00+0     doi:10.1128/MCB.01075-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhuang, J., Jiang, G., Willers, H., Xia, F. (2009). Exonuclease Function of Human Mre11 Promotes Deletional Nonhomologous End Joining. J. Biol. Chem. 284: 30565-30573 [Abstract] [Full Text]  


Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»