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 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.
Mantel
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Department of Microbiology/Immunology, Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, IN 46202-5121, USA. cmantel@iupui.edu
Braun
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SE
Lee
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Kim
Y J
YJ
Broxmeyer
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HE
D000818:Animals; D016203:CDC2 Protein Kinase / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000187:drug effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000494:pharmacology*; D004247:DNA / Q000378:metabolism; D006801:Humans; D007399:Interphase / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000473:pathology* / Q000502:physiology; D016196:S Phase; D014407:Tumor Cells, Cultured
C493956:CDKN1A protein, human; C493957:Cdkn1a protein, mouse; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004247:DNA; D016203:CDC2 Protein Kinase