Abnormal centrosome amplification in the absence of p53

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

Research output: Contribution to journalArticlepeer-review

705 Scopus citations

Abstract

The centrosome plays a vital role in mitotic fidelity, ensuring establishment of bipolar spindles and balances chromosome segregation. Centrosome duplication occurs only once during 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 functinally 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 centrosomic 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.

Original languageEnglish (US)
Pages (from-to)1744-1747
Number of pages4
JournalScience
Volume271
Issue number5256
DOIs
StatePublished - Mar 22 1996

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