The interphase microtubule damage checkpoint defines an S-phase commitment point and does not require p21waf-1

Abstract

Cell cycle checkpoints ensure orderly progression of events during cell division. A microtubule damage (MTD)-induced checkpoint has been described in G1 phase of the cell cycle (G1MTC) for which little is known. The present study shows that the G1MTC is intact in activated T lymphocytes from mice with the p21waf-1 gene deleted. However, p21waf-1 gene deletion does affect the ratio of cells that arrest at the G1MTC and the spindle checkpoint after MTD. The G1MTC arrests T lymphocytes in G1 prior to cdc2 up-regulation and prior to G1 arrest by p21waf-1. Once cells have progressed past the G1MTC, they are committed to chromosome replication and metaphase progression, even with extreme MTD. The G1MTC is also present in a human myeloid cell line deficient in p21waf-1 gene expression. The p21-independent G1MTC may be important in cellular responses to MTD such as those induced by drugs used to treat cancer. © 2001 by The American Society of Hematology.