Cell cycle progression is subject to arrest at the mitotic spindle assembly checkpoint in response to incorrect spindle fiber assembly. MAD1 and MAD2 (for mitotic arrest-deficient 1 and 2) are components of the mitotic spindle checkpoint. Incorrect spindle assembly in normal cells leads to mitotic arrest. MAD1 prevents the onset of anaphase until all chromosomes are aligned correctly at the metaphase plate and is crucial for anchoring MAD2L1 to the nuclear periphery. It also plays an important role in septum positioning. MAD1 can form a homo-dimer, but may also form a heterodimer with MAD2 to form the tetrameric MAD1L1-MAD2L1 core complex. MAD1 localizes primarily to the nucleus, but during mitosis, it moves from a nuclear distribution to the centrosome, to the spindle midzone and then on to the midbody. MAD1 activity is induced by BUB1 and the protein is hyperphosphorylated after mitotic spindle damage and/or in late S through M phase. Defects in the gene encoding for MAD1, MAD1L1, play a major role in the development and progression of various cancer types.
