MAD2 haplo-insufficiency causes premature anaphase and chromosome instability in mammalian cells

摘要: The mitotic checkpoint protein hsMad2 is required to arrest cells in mitosis when chromosomes are unattached the spindle. presence of a single, lagging chromosome sufficient activate checkpoint, producing delay at metaphase-anaphase transition until last spindle attachment made. Complete loss results embryonic lethality owing mis-segregation various organisms. Whether partial control leads more subtle rates instability compatible with cell viability remains unknown. Here we report that deletion one MAD2 allele defective both human cancer and murine primary fibroblasts. Checkpoint-defective show premature sister-chromatid separation inhibitors an elevated rate events absence these agents. Furthermore, Mad2+/- mice develop lung tumours high after long latencies, implicating defects tumorigenesis.