Published online 6 March 2006
Survey and Summary |
BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution
Genetics of Development and Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health 10/9N105, 10 Center Drive, Bethesda, MD 20892, USA
*To whom correspondence should be addressed. Tel: +1 301 402 7225; Fax: +1 301 480 1135; Email: chuxiad{at}bdg10.niddk.nih.gov
Received February 11, 2006. Accepted February 11, 2006.
Germline mutations of the breast cancer associated gene 1 (BRCA1) predispose women to breast and ovarian cancers. BRCA1 is a large protein with multiple functional domains and interacts with numerous proteins that are involved in many important biological processes/pathways. Mounting evidence indicates that BRCA1 is involved in all phases of the cell cycle and regulates orderly events during cell cycle progression. BRCA1 deficiency, consequently causes abnormalities in the S-phase checkpoint, the G2/M checkpoint, the spindle checkpoint and centrosome duplication. The genetic instability caused by BRCA1 deficiency, however, also triggers cellular responses to DNA damage that blocks cell proliferation and induces apoptosis. Thus BRCA1 mutant cells cannot develop further into full-grown tumors unless this cellular defense is broken. Functional analysis of BRCA1 in cell cycle checkpoints, genome integrity, DNA damage response (DDR) and tumor evolution should benefit our understanding of the mechanisms underlying BRCA1 associated tumorigenesis, as well as the development of therapeutic approaches for this lethal disease.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J.-R. Weng, C.-H. Tsai, H. A. Omar, A. M. Sargeant, D. Wang, S. K. Kulp, C. L. Shapiro, and C.-S. Chen OSU-A9, a potent indole-3-carbinol derivative, suppresses breast tumor growth by targeting the Akt-NF-{kappa}B pathway and stress response signaling Carcinogenesis, October 1, 2009; 30(10): 1702 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. De Nicolo, E. Parisini, Q. Zhong, M. Dalla Palma, K. A. Stoeckert, S. M. Domchek, K. L. Nathanson, M. A. Caligo, M. Vidal, M. E. Cusick, et al. Multimodal Assessment of Protein Functional Deficiency Supports Pathogenicity of BRCA1 p.V1688del Cancer Res., September 1, 2009; 69(17): 7030 - 7037. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Holstege, S. A. Joosse, C. Th. M. van Oostrom, P. M. Nederlof, A. de Vries, and J. Jonkers High Incidence of Protein-Truncating TP53 Mutations in BRCA1-Related Breast Cancer Cancer Res., April 15, 2009; 69(8): 3625 - 3633. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-l. Ding, J.-C. Yu, S.-T. Chen, G.-C. Hsu, S.-J. Kuo, Y. H. Lin, P.-E. Wu, and C.-Y. Shen Genetic variants of BLM interact with RAD51 to increase breast cancer susceptibility Carcinogenesis, January 1, 2009; 30(1): 43 - 49. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. J. Reid, R. Shakya, A. P. Modi, M. Lokshin, J.-T. Cheng, M. Jasin, R. Baer, and T. Ludwig E3 ligase activity of BRCA1 is not essential for mammalian cell viability or homology-directed repair of double-strand DNA breaks PNAS, December 30, 2008; 105(52): 20876 - 20881. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Xiong, S. Li, J.-S. Ai, S. Yin, Y.-C. OuYang, S.-C. Sun, D.-Y. Chen, and Q.-Y. Sun BRCA1 Is Required for Meiotic Spindle Assembly and Spindle Assembly Checkpoint Activation in Mouse Oocytes Biol Reprod, October 1, 2008; 79(4): 718 - 726. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Fox III, I. Le Trong, P. Rajagopal, P. S. Brzovic, R. E. Stenkamp, and R. E. Klevit Crystal Structure of the BARD1 Ankyrin Repeat Domain and Its Functional Consequences J. Biol. Chem., July 25, 2008; 283(30): 21179 - 21186. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Hu, Y. Liu, C. Zhang, Y. Zhao, W. He, L. Han, L. Yang, K. M. Hopkins, X. Yang, H. B. Lieberman, et al. Targeted Deletion of Rad9 in Mouse Skin Keratinocytes Enhances Genotoxin-Induced Tumor Development Cancer Res., July 15, 2008; 68(14): 5552 - 5561. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L Komarova, A. V Sadovsky, and F. Y.M Wan Selective pressures for and against genetic instability in cancer: a time-dependent problem J R Soc Interface, January 6, 2008; 5(18): 105 - 121. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Laufer, S. V. Nandula, A. P. Modi, S. Wang, M. Jasin, V. V. V. S. Murty, T. Ludwig, and R. Baer Structural Requirements for the BARD1 Tumor Suppressor in Chromosomal Stability and Homology-directed DNA Repair J. Biol. Chem., November 23, 2007; 282(47): 34325 - 34333. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Deeb, A. M. Michalowska, C.-y. Yoon, S. M. Krummey, M. J. Hoenerhoff, C. Kavanaugh, M.-c. Li, F. J. Demayo, I. Linnoila, C.-x. Deng, et al. Identification of an Integrated SV40 T/t-Antigen Cancer Signature in Aggressive Human Breast, Prostate, and Lung Carcinomas with Poor Prognosis Cancer Res., September 1, 2007; 67(17): 8065 - 8080. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Macaluso, M. Montanari, P. B. Noto, V. Gregorio, C. Bronner, and A. Giordano Epigenetic Modulation of Estrogen Receptor-{alpha} by pRb Family Proteins: A Novel Mechanism in Breast Cancer Cancer Res., August 15, 2007; 67(16): 7731 - 7737. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yan, Y.-S. Kim, X.-P. Yang, L.-P. Li, G. Liao, F. Xia, and A. M. Jetten The Ubiquitin-Interacting Motif Containing Protein RAP80 Interacts with BRCA1 and Functions in DNA Damage Repair Response Cancer Res., July 15, 2007; 67(14): 6647 - 6656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Lin, C.-C. Liu, Q. Gao, X. Zhang, G. Wu, and W.-H. Lee RINT-1 Serves as a Tumor Suppressor and Maintains Golgi Dynamics and Centrosome Integrity for Cell Survival Mol. Cell. Biol., July 1, 2007; 27(13): 4905 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Cao, X. Xu, L. L. Cao, R.-H. Wang, X. Coumoul, S. S. Kim, and C.-X. Deng Absence of full-length Brca1 sensitizes mice to oxidative stress and carcinogen-induced tumorigenesis in the esophagus and forestomach Carcinogenesis, July 1, 2007; 28(7): 1401 - 1407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-C. Wang, M.-F. Tsai, T.-H. Dai, T.-M. Hong, W.-K. Chan, J. J.W. Chen, and P.-C. Yang Synergistic Activation of the Tumor Suppressor, HLJ1, by the Transcription Factors YY1 and Activator Protein 1 Cancer Res., May 15, 2007; 67(10): 4816 - 4826. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Holzel, T. Grimm, M. Rohrmoser, A. Malamoussi, T. Harasim, A. Gruber-Eber, E. Kremmer, and D. Eick The BRCT domain of mammalian Pes1 is crucial for nucleolar localization and rRNA processing Nucleic Acids Res., February 16, 2007; 35(3): 789 - 800. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. DelloRusso, P. L. Welcsh, W. Wang, R. L. Garcia, M.-C. King, and E. M. Swisher Functional Characterization of a Novel BRCA1-Null Ovarian Cancer Cell Line in Response to Ionizing Radiation Mol. Cancer Res., January 1, 2007; 5(1): 35 - 45. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Lord, M. D. Garrett, and A. Ashworth Targeting the Double-Strand DNA Break Repair Pathway as a Therapeutic Strategy Clin. Cancer Res., August 1, 2006; 12(15): 4463 - 4468. [Abstract] [Full Text] [PDF]
|
|