Cell cycle progression is subject to arrest at the mitotic spindle assembly checkpoint in response to incorrect spindle fiber assembly. MAD2 (for mitotic arrest-deficient) is a component of the mitotic spindle checkpoint. Cells with mutated MAD2 do not undergo mitotic arrest in response to incorrect spindle fiber assembly, which results in missegregation and eventual cell death. A breast carcinoma cell line with reduced MAD2 expression, T47D, was shown to complete mitosis in the presence of nocodazole, an inhibitor of mitotic spindle assembly. MAD2 is localized to unattached kinetochores during prometaphase and disassociates upon spindle fiber attachment, indicating that MAD2 regulates kinetochore binding to the spindle fibers.
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