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TY - JOUR AU - Michel, Loren S. AU - Liberal, Vasco AU - Chatterjee, Anupam AU - Kirchwegger, Regina AU - Pasche, Boris AU - Gerald, William AU - Dobles, Max AU - Sorger, Peter K. AU - Murty, V. V. V. S. AU - Benezra, Robert PY - 2001 DA - 2001/01/01 TI - MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells JO - Nature SP - 355 EP - 359 VL - 409 IS - 6818 AB - The mitotic checkpoint protein hsMad2 is required to arrest cells in mitosis when chromosomes are unattached to the mitotic spindle1. The presence of a single, lagging chromosome is sufficient to activate the checkpoint, producing a delay at the metaphase–anaphase transition until the last spindle attachment is made2. Complete loss of the mitotic checkpoint results in embryonic lethality owing to chromosome mis-segregation in various organisms3,4,5,6. Whether partial loss of checkpoint control leads to more subtle rates of chromosome instability compatible with cell viability remains unknown. Here we report that deletion of one MAD2 allele results in a defective mitotic checkpoint in both human cancer cells and murine primary embryonic fibroblasts. Checkpoint-defective cells show premature sister-chromatid separation in the presence of spindle inhibitors and an elevated rate of chromosome mis-segregation events in the absence of these agents. Furthermore, Mad2+/- mice develop lung tumours at high rates after long latencies, implicating defects in the mitotic checkpoint in tumorigenesis. SN - 1476-4687 UR - https://doi.org/10.1038/35053094 DO - 10.1038/35053094 ID - Michel2001 ER -