Abstract
Cell cycle checkpoints enhance genetic fidelity by causing arrest at specific stages of the cell cycle when previous events have not been completed. The tumor suppressor p53 has been implicated in a G1 checkpoint. To investigate whether p53 also participates in a mitotic checkpoint, cultured fibroblasts from p53-deficient mouse embryos were exposed to spindle inhibitors. The fibroblasts underwent multiple rounds of DNA synthesis without completing chromosome segregation, thus forming tetraploid and octaploid cells. Deficiency of p53 was also associated with the development of tetraploidy in vivo. These results suggest that murine p53 is a component of a spindle checkpoint that ensures the maintenance of diploidy.
References
53
Referenced
503
-
ARNDTJOVIN, D.J., ANALYSIS AND SORTING OF LIVING CELLS ACCORDING TO DEOXYRIBONUCLEIC-ACID CONTENT, JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY 25: 585 (1977).
(
10.1177/25.7.70450
) / JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY (1977) 10.1126/science.2649981
- Barber, H. N., Proceedings of the Royal Society of London B 131: 258 (1943). / Proceedings of the Royal Society of London B (1943)
- BLOUNT, P.L., 17P ALLELIC LOSSES IN DIPLOID-CELLS OF PATIENTS WITH BARRETTS-ESOPHAGUS WHO DEVELOP ANEUPLOIDY, CANCER RESEARCH 54: 2292 (1994). / CANCER RESEARCH (1994)
-
BROEK, D, INVOLVEMENT OF P34CDC2 IN ESTABLISHING THE DEPENDENCY OF S-PHASE ON MITOSIS, NATURE 349: 388 (1991).
(
10.1038/349388a0
) / NATURE (1991) -
BROWN, M, FIDELITY OF MITOTIC CHROMOSOME TRANSMISSION, COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY 56: 359 (1991).
(
10.1101/SQB.1991.056.01.043
) / COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY (1991) -
BUNN, P.A., FLOW CYTOMETRIC ANALYSIS OF DNA CONTENT OF BONE-MARROW CELLS IN PATIENTS WITH PLASMA-CELL MYELOMA - CLINICAL IMPLICATIONS, BLOOD 59: 528 (1982).
(
10.1182/blood.V59.3.528.528
) / BLOOD (1982) - BURHOLT, D.R., KARYOTYPIC EVOLUTION OF A HUMAN UNDIFFERENTIATED LARGE CELL-CARCINOMA OF THE LUNG IN TISSUE-CULTURE, CANCER RESEARCH 49: 3355 (1989). / CANCER RESEARCH (1989)
- CARDER, P, STABILIZED P53 FACILITATES ANEUPLOID CLONAL DIVERGENCE IN COLORECTAL-CANCER, ONCOGENE 8: 1397 (1993). / ONCOGENE (1993)
10.1016/0092-8674(90)90191-G
- GONG, J, CANCER RESEARCH 54: 4285 (1994). / CANCER RESEARCH (1994)
-
HARTWELL, L.H., ALTERED FIDELITY OF MITOTIC CHROMOSOME TRANSMISSION IN CELL-CYCLE MUTANTS OF S-CEREVISIAE, GENETICS 110: 381 (1985).
(
10.1093/genetics/110.3.381
) / GENETICS (1985) 10.1126/science.183.4120.46
10.1126/science.2683079
- HARVEY, M, IN-VITRO GROWTH-CHARACTERISTICS OF EMBRYO FIBROBLASTS ISOLATED FROM P53-DEFICIENT MICE, ONCOGENE 8: 2457 (1993). / ONCOGENE (1993)
10.1126/science.1905840
10.1016/0092-8674(81)90014-3
-
JACKS, T, TUMOR SPECTRUM ANALYSIS IN P53-MUTANT MICE, CURRENT BIOLOGY 4: 1 (1994).
(
10.1016/S0960-9822(00)00002-6
) / CURRENT BIOLOGY (1994) -
JAKOBSEN, A, CHARACTERIZATION OF PLOIDY LEVEL IN BLADDER-TUMORS AND SELECTED SITE SPECIMENS BY FLOW-CYTOMETRY, CYTOMETRY 4: 170 (1983).
(
10.1002/cyto.990040211
) / CYTOMETRY (1983) - KASTAN, M.B., PARTICIPATION OF P53 PROTEIN IN THE CELLULAR-RESPONSE TO DNA DAMAGE, CANCER RESEARCH 51: 6304 (1991). / CANCER RESEARCH (1991)
10.1016/0092-8674(92)90593-2
-
KIRKLAND, J.A., COMPARATIVE STUDY OF HISTOLOGIC AND CHROMOSOMAL ABNORMALITIES IN CERVICAL NEOPLASIA, CANCER 20: 1934 (1967).
(
10.1002/1097-0142(196711)20:11<1934::AID-CNCR2820201122>3.0.CO;2-4
) / CANCER (1967) - KNOEFEL, W.T., CANCER RES 47: 221 (1987). / CANCER RES (1987)
- KUERBITZ, S.J., WILD-TYPE P53 IS A CELL-CYCLE CHECKPOINT DETERMINANT FOLLOWING IRRADIATION, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 89: 7491 (1992). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1992)
- KUHAR, S.G., T-ANTIGEN AND P53 IN PRECRISIS AND POSTCRISIS SIMIAN VIRUS-40-TRANSFORMED HUMAN CELL-LINES, ONCOGENE 6: 1499 (1991). / ONCOGENE (1991)
- KUNG, A.L., CELL LINE-SPECIFIC DIFFERENCES IN THE CONTROL OF CELL-CYCLE PROGRESSION IN THE ABSENCE OF MITOSIS, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 87: 9553 (1990). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1990)
-
LAFFIN, J, CORRELATION OF DNA CONTENT, P53, T-ANTIGEN, AND V-ANTIGEN IN SIMIAN VIRUS-40-INFECTED HUMAN-DIPLOID CELLS, CYTOMETRY 10: 205 (1989).
(
10.1002/cyto.990100212
) / CYTOMETRY (1989) 10.1038/278261a0
-
LEVAN, A, CHROMOSOMES IN CANCER TISSUE, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES 63: 774 (1956).
(
10.1111/j.1749-6632.1956.tb50892.x
) / ANNALS OF THE NEW YORK ACADEMY OF SCIENCES (1956) -
LEVINE, A.J., THE P53 TUMOR SUPPRESSOR GENE, NATURE 351: 453 (1991).
(
10.1038/351453a0
) / NATURE (1991) - LEVINE, D.S., FORMATION OF THE TETRAPLOID INTERMEDIATE IS ASSOCIATED WITH THE DEVELOPMENT OF CELLS WITH MORE THAN 4 CENTRIOLES IN THE ELASTASE SIMIAN VIRUS-40 TUMOR-ANTIGEN TRANSGENIC MOUSE MODEL OF PANCREATIC-CANCER, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 88: 6427 (1991). / PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (1991)
10.1016/0092-8674(81)90015-5
-
LIEBMANN, J, THE INFLUENCE OF CREMOPHOR EL ON THE CELL-CYCLE EFFECTS OF PACLITAXEL (TAXOL(R)) IN HUMAN TUMOR-CELL LINES, CANCER CHEMOTHERAPY AND PHARMACOLOGY 33: 331 (1994).
(
10.1007/BF00685909
) / CANCER CHEMOTHERAPY AND PHARMACOLOGY (1994) 10.1016/0092-8674(79)90293-9
10.1016/0092-8674(92)90243-6
-
LOPES, N.M., CELL KILL KINETICS AND CELL-CYCLE EFFECTS OF TAXOL ON HUMAN AND HAMSTER OVARIAN CELL-LINES, CANCER CHEMOTHERAPY AND PHARMACOLOGY 32: 235 (1993).
(
10.1007/BF00685842
) / CANCER CHEMOTHERAPY AND PHARMACOLOGY (1993) -
LU, X, DIFFERENTIAL INDUCTION OF TRANSCRIPTIONALLY ACTIVE P53 FOLLOWING UV OR IONIZING-RADIATION - DEFECTS IN CHROMOSOME INSTABILITY SYNDROMES, CELL 75: 765 (1993).
(
10.1016/0092-8674(93)90496-D
) / CELL (1993) -
MURRAY, A.W., COORDINATING CELL-CYCLE EVENTS, COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY 56: 399 (1991).
(
10.1101/SQB.1991.056.01.047
) / COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY (1991) -
NESHAT, K, P53 MUTATIONS IN BARRETTS ADENOCARCINOMA AND HIGH-GRADE DYSPLASIA, GASTROENTEROLOGY 106: 1589 (1994).
(
10.1016/0016-5085(94)90415-4
) / GASTROENTEROLOGY (1994) -
OFFERHAUS, GJA, THE RELATIONSHIP OF DNA ANEUPLOIDY TO MOLECULAR GENETIC ALTERATIONS IN COLORECTAL-CARCINOMA, GASTROENTEROLOGY 102: 1612 (1992).
(
10.1016/0016-5085(92)91721-F
) / GASTROENTEROLOGY (1992) 10.1126/science.2821617
-
Ramel, S., Pancreas 11: 213 (1995).
(
10.1097/00006676-199510000-00001
) / Pancreas (1995) - RASKIND, W.H., PERSISTENT CLONAL AREAS AND CLONAL EXPANSION IN BARRETTS-ESOPHAGUS, CANCER RESEARCH 52: 2946 (1992). / CANCER RESEARCH (1992)
- Reider, C. L., Mechanisms of Chromosome Distribution and Aneuploidy: 185 (1989). / Mechanisms of Chromosome Distribution and Aneuploidy (1989)
- ROBERTS, J.R., DEVELOPMENT OF POLYPLOIDIZATION IN TAXOL-RESISTANT HUMAN LEUKEMIA-CELLS INVITRO, CANCER RESEARCH 50: 710 (1990). / CANCER RESEARCH (1990)
-
SCHIMKE, R.T., DIFFERENCES IN MITOTIC CONTROL AMONG MAMMALIAN-CELLS, COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY 56: 417 (1991).
(
10.1101/SQB.1991.056.01.049
) / COLD SPRING HARBOR SYMPOSIA ON QUANTITATIVE BIOLOGY (1991) - SHACKNEY, S.E., MODEL FOR THE GENETIC EVOLUTION OF HUMAN SOLID TUMORS, CANCER RESEARCH 49: 3344 (1989). / CANCER RESEARCH (1989)
-
SHAPIRO, J.R., THE SUBPOPULATIONS AND ISOLATED CELL-TYPES OF FRESHLY RESECTED HIGH-GRADE HUMAN GLIOMAS - THEIR INFLUENCE ON THE TUMORS EVOLUTION INVIVO AND BEHAVIOR AND THERAPY INVITRO, CANCER AND METASTASIS REVIEWS 4: 107 (1985).
(
10.1007/BF00050691
) / CANCER AND METASTASIS REVIEWS (1985) -
WANG, R.J., FURTHER-STUDIES ON A MUTANT MAMMALIAN-CELL LINE DEFECTIVE IN MITOSIS, EXPERIMENTAL CELL RESEARCH 101: 331 (1976).
(
10.1016/0014-4827(76)90385-2
) / EXPERIMENTAL CELL RESEARCH (1976) 10.1126/science.3291120
-
WIJKSTROM, H, CHROMOSOMAL AND DNA PATTERNS IN TRANSITIONAL CELL BLADDER-CARCINOMA - A COMPARATIVE CYTOGENETIC AND FLOW-CYTOFLUOROMETRIC DNA STUDY, CANCER 53: 1718 (1984).
(
10.1002/1097-0142(19840415)53:8<1718::AID-CNCR2820530817>3.0.CO;2-E
) / CANCER (1984) -
YIN, Y.X., WILD-TYPE P53 RESTORES CELL-CYCLE CONTROL AND INHIBITS GENE AMPLIFICATION IN CELLS WITH MUTANT P53 ALLELES, CELL 70: 937 (1992).
(
10.1016/0092-8674(92)90244-7
) / CELL (1992) -
ZIRKLE, R.E., ULTRAVIOLET-MICROBEAM IRRADIATION OF NEWT-CELL CYTOPLASM - SPINDLE DESTRUCTION, FALSE ANAPHASE, AND DELAY OF TRUE ANAPHASE, RADIATION RESEARCH 41: 516 (1970).
(
10.2307/3572841
) / RADIATION RESEARCH (1970)
Dates
Type | When |
---|---|
Created | 18 years, 9 months ago (Oct. 27, 2006, 2:19 p.m.) |
Deposited | 1 year, 7 months ago (Jan. 14, 2024, 11:24 p.m.) |
Indexed | 1 month, 1 week ago (July 16, 2025, 7:50 a.m.) |
Issued | 30 years, 5 months ago (March 3, 1995) |
Published | 30 years, 5 months ago (March 3, 1995) |
Published Print | 30 years, 5 months ago (March 3, 1995) |
@article{Cross_1995, title={A p53-Dependent Mouse Spindle Checkpoint}, volume={267}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.7871434}, DOI={10.1126/science.7871434}, number={5202}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Cross, Shawn M. and Sanchez, Carissa A. and Morgan, Catherine A. and Schimke, Melana K. and Ramel, Stig and Idzerda, Rejean L. and Raskind, Wendy H. and Reid, Brian J.}, year={1995}, month=mar, pages={1353–1356} }