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Science 22 March 1996:
Vol. 271. no. 5256, pp. 1744 - 1747
DOI: 10.1126/science.271.5256.1744

Reports

Abnormal Centrosome Amplification in the Absence of p53

Kenji Fukasawa, Taesaeng Choi, Ryoko Kuriyama, Shen Rulong, George F. Vande Woude *

The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balanced chromosome segregation. Centrosome duplication occurs only once during the cell cycle and is therefore highly regulated. Here, it is shown that in mouse embryonic fibroblasts (MEFs) lacking the p53 tumor suppressor protein, multiple copies of functionally competent centrosomes are generated during a single cell cycle. In contrast, MEFs prepared from normal mice or mice deficient in the retinoblastoma tumor suppressor gene product do not display these abnormalities. The abnormally amplified centrosomes profoundly affect mitotic fidelity, resulting in unequal segregation of chromosomes. These observations implicate p53 in the regulation of centrosome duplication and suggest one possible mechanism by which the loss of p53 may cause genetic instability.

K. Fukasawa, T. Choi, S. Rulong, G. F. Vande Woude, ABL-Basic Research Program, National Cancer Institute, Frederick Cancer Research and Development Center, Post Office Box B, Frederick, MD 21702-1201, USA.
R. Kuriyama, Department of Cell Biology and Neuroanatomy, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
* To whom correspondence should be adressed.



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   Abstract »    Full Text »    PDF »
Genetic and Hormonal Risk Factors in Breast Cancer.
A.-M. Martin and B. L. Weber (2000)
J Natl Cancer Inst 92, 1126-1135
   Abstract »    Full Text »    PDF »
Chromosome instability contributes to loss of heterozygosity in mice lacking p53.
C. Shao, L. Deng, O. Henegariu, L. Liang, P. J. Stambrook, and J. A. Tischfield (2000)
PNAS 97, 7405-7410
   Abstract »    Full Text »    PDF »
Cancer Risk and the ATM Gene: a Continuing Debate.
K. K. Khanna (2000)
J Natl Cancer Inst 92, 795-802
   Abstract »    Full Text »    PDF »
Retinoblastoma Protein Enhances the Fidelity of Chromosome Segregation Mediated by hsHec1p.
L. Zheng, Y. Chen, D. J. Riley, P.-L. Chen, and W.-H. Lee (2000)
Mol. Cell. Biol. 20, 3529-3537
   Abstract »    Full Text »    PDF »
XCS-1, a maternally expressed gene product involved in regulating mitosis in Xenopus.
H Nakamura, C Wu, J Kuang, C Larabell, and L. Etkin (2000)
J. Cell Sci. 113, 2497-2505
   Abstract »    PDF »
Role of DNA Break-sensing Molecule Poly(ADP-ribose) Polymerase (PARP) in Cellular Function and Radiation Toxicity.
W.-M. TONG, D. GALENDO, and Z.-Q. WANG (2000)
Cold Spring Harb Symp Quant Biol 65, 583-592
   Abstract »    PDF »
MAPK Mediates RAS-induced Chromosome Instability.
H. I. Saavedra, K. Fukasawa, C. W. Conn, and P. J. Stambrook (1999)
J. Biol. Chem. 274, 38083-38090
   Abstract »    Full Text »    PDF »
Defects in transforming growth factor-beta signaling cooperate with a Ras oncogene to cause rapid aneuploidy and malignant transformation of mouse keratinocytes.
A. Glick, N. Popescu, V. Alexander, H. Ueno, E. Bottinger, and S. H. Yuspa (1999)
PNAS 96, 14949-14954
   Abstract »    Full Text »    PDF »
Altered Centrosome Structure Is Associated with Abnormal Mitoses in Human Breast Tumors.
W. L. Lingle and J. L. Salisbury (1999)
Am. J. Pathol. 155, 1941-1951
   Abstract »    Full Text »    PDF »
Chromosomal aberrations in PARP-/- mice: Genome stabilization in immortalized cells by reintroduction of poly(ADP-ribose) polymerase cDNA.
C. M. Simbulan-Rosenthal, B. R. Haddad, D. S. Rosenthal, Z. Weaver, A. Coleman, R. Luo, H. M. Young, Z.-Q. Wang, T. Ried, and M. E. Smulson (1999)
PNAS 96, 13191-13196
   Abstract »    Full Text »    PDF »
Disruption of the ARF-Mdm2-p53 tumor suppressor pathway in Myc-induced lymphomagenesis.
C. M. Eischen, J. D. Weber, M. F. Roussel, C. J. Sherr, and J. L. Cleveland (1999)
Genes & Dev. 13, 2658-2669
   Abstract »    Full Text »
Components of an SCF ubiquitin ligase localize to the centrosome and regulate the centrosome duplication cycle.
E. Freed, K. R. Lacey, P. Huie, S. A. Lyapina, R. J. Deshaies, T. Stearns, and P. K. Jackson (1999)
Genes & Dev. 13, 2242-2257
   Abstract »    Full Text »
How many tumor suppressor genes are involved in human lung carcinogenesis?.
T. Kohno and J. Yokota1 (1999)
Carcinogenesis 20, 1403-1410
   Abstract »    Full Text »    PDF »
Apoptotic and Mitotic Indices Predict Survival Rates in Lymph Node-negative Colon Carcinomas.
F. A. Sinicrope, J. Hart, H.-A. Hsu, M. Lemoine, F. Michelassi, and L. C. Stephens (1999)
Clin. Cancer Res. 5, 1793-1804
   Abstract »    Full Text »    PDF »
Budding Yeast Bub2 Is Localized at Spindle Pole Bodies and Activates the Mitotic Checkpoint via a Different Pathway from Mad2.
R. Fraschini, E. Formenti, G. Lucchini, and S. Piatti (1999)
J. Cell Biol. 145, 979-991
   Abstract »    Full Text »    PDF »
Centrosome Abnormalities in Pancreatic Ductal Carcinoma.
N. Sato, K. Mizumoto, M. Nakamura, K. Nakamura, M. Kusumoto, H. Niiyama, T. Ogawa, and M. Tanaka (1999)
Clin. Cancer Res. 5, 963-970
   Abstract »    Full Text »    PDF »
Roles of the functional loss of p53 and other genes inastrocytoma tumorigenesis and progression.
M. Nozaki, M. Tada, H. Kobayashi, C.-L. Zhang, Y. Sawamura, H. Abe, N. Ishii, and E. G. Van Meir (1999)
Neuro Oncology 1, 124-137
   Abstract »    PDF »



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