MAD1 is a non-essential gene that encodes a component of the spindle checkpoint (4, 2). The spindle checkpoint delays the onset of anaphase in cells with defects in mitotic spindle assembly or in the attachment o f chromosomes to the spindle microtubules (see 5 for review; reference 6 describes defects detected by the c heckpoint). The checkpoint works by inhibiting the activity of the anaphase promoting complex, thereby preventing the degradation of several cell cycl e regulators (5). Like other spindle checkpoint mutants, mad1 loss-of-function mutants are sensitive to benomyl and cannot delay cell division in response to spindle depolymerization (4, 2). Mad1p becomes hyperphosphorylated upon spindle depolymerization (2). The essential protein kinase Msp 1p is involved in the spindle checkpoint, and appears to phosphorylate Mad1p (1,7). Mad1p forms a tight complex with another spindle checkpoint protein, Mad2p, throughout the cell cycle (8). Mad1p interacts with Cdc20p, which activates the anaphase promoting complex, in the two-hybrid system, and the presence of Mad1p is required for Mad2 p and Mad3p to interact with Cdc20p (9). Bub1p, Bub3p, Mad1p, Mad2p, Mad3p, and Mps1p act in a branch of the spindle checkpoint pathway that may prevent premature chromosome disjunction. A second branch involves Bub2p and Bfa1p, and may prevent cytokinesis prior to chromosome segregation(10, 11, 12, 13). Homologs of Mad1p act in the spindle checkpoint in Xenopus (Xmad1; 14) and human (MAD1L1; 15).

Last updated: 2005-07-01