The interphase microtubule damage checkpoint defines an S-phase commitment point and does not require p21(waf-1)

Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of the cell cycle (G(1)MTC) for which little is known. The present study shows that the G(1)MTC is intact in activated T lymphocytes from m...

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Bibliographic Details
Published in:Blood 2001-03, Vol.97 (5), p.1505-1507
Main Authors: Mantel, C R, Braun, S E, Lee, Y, Kim, Y J, Broxmeyer, H E
Format: Article
Language:English
Subjects:
Animals
CDC2 Protein Kinase - metabolism
Cell Cycle Proteins - drug effects
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - pharmacology
DNA - metabolism
Humans
Interphase - genetics
Interphase - physiology
Mice
Mice, Knockout
Microtubules - pathology
Microtubules - physiology
S Phase
Tumor Cells, Cultured
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Summary:Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G(1) phase of the cell cycle (G(1)MTC) for which little is known. The present study shows that the G(1)MTC is intact in activated T lymphocytes from mice with the p21(waf-1) gene deleted. However, p21(waf-1) gene deletion does affect the ratio of cells that arrest at the G(1)MTC and the spindle checkpoint after MTD. The G(1)MTC arrests T lymphocytes in G(1) prior to cdc2 up-regulation and prior to G(1) arrest by p21(waf-1). Once cells have progressed past the G(1)MTC, they are committed to chromosome replication and metaphase progression, even with extreme MTD. The G(1)MTC is also present in a human myeloid cell line deficient in p21(waf-1) gene expression. The p21-independent G(1)MTC may be important in cellular responses to MTD such as those induced by drugs used to treat cancer.
ISSN:0006-4971
DOI:10.1182/blood.V97.5.1505