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

Cell cycle checkpoints ensure orderly progression of events during cell div ision. 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 prese nt study shows that the G(1)MTC is intact in activated T lymphocytes from m ice with the p21(waf-1) gene deleted. However, p21(waf-1) gene deletion doe s affect the ratio of cells that arrest at the G(1)MTC and the spindle chec kpoint after MTD. The G(1)MTC arrests T lymphocytes in G(1) prior to cdc2 u p-regulation and prior to G(1) arrest by p21(waf-1). Once cells have progre ssed past the G(1)MTC, they are committed to chromosome replication and met aphase 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-i ndependent G(1)MTC may be important in cellular responses to MTD such as th ose induced by drugs used to treat cancer. (Blood, 2001;97:1505-1507) (C) 2 001 by The American Society of Hematology.