Published 7 June 2004. doi:10.1083/jcb.200403014
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 5, 609-615
Cell cycle progression after cleavage failure
:
mammalian somatic cells do not possess a "tetraploidy checkpoint"
Yumi Uetake and
Greenfield Sluder
Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA 01605
Address correspondence to Greenfield Sluder, University of Massachusetts Medical School, Biotech 4, 3rd floor, 377 Plantation St., Worcester, MA 01605. Tel.: (508) 856-8651. Fax: (508) 856-8774. email: Greenfield.Sluder{at}umassmed.edu
Failure of cells to cleave at the end of mitosis is dangerous to the organism because it immediately produces tetraploidy and centrosome amplification, which is thought to produce genetic imbalances. Using normal human and rat cells, we reexamined the basis for the attractive and increasingly accepted proposal that normal mammalian cells have a "tetraploidy checkpoint" that arrests binucleate cells in G1, thereby preventing their propagation. Using 10 µM cytochalasin to block cleavage, we confirm that most binucleate cells arrest in G1. However, when we use lower concentrations of cytochalasin, we find that binucleate cells undergo DNA synthesis and later proceed through mitosis in >80% of the cases for the hTERT-RPE1 human cell line, primary human fibroblasts, and the REF52 cell line. These observations provide a functional demonstration that the tetraploidy checkpoint does not exist in normal mammalian somatic cells.
Key Words: cell cycle; checkpoint; cleavage; cytokinesis; tetraploidy
The online version of this article includes supplemental material.

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