MAD2 ASSOCIATES WITH THE CYCLOSOME ANAPHASE-PROMOTING COMPLEX AND INHIBITS ITS ACTIVITY/

Cell cycle progression is monitored by checkpoint mechanisms that ensu re faithful duplication and accurate segregation of the genome. Defect s in spindle assembly or spindle-kinetochore attachment activate the m itotic checkpoint, Once activated, this checkpoint arrests cells prior to the metaphase-anaphase transition with unsegregated chromosomes, s table cyclin B, and elevated M phase promoting factor activity, Howeve r, the mechanisms underlying this process remain obscure, Here we repo rt that upon activation of the mitotic checkpoint, MAD2, an essential component of the mitotic checkpoint, associates with the cyclin B-ubiq uitin ligase, known as the cyclosome or anaphase-promoting complex, Mo reover, purified MAD2 causes a metaphase arrest in cycling Xenopus lae vis egg extracts and prevents cyclin B proteolysis by blocking its ubi quitination, indicating that MAD2 functions as an inhibitor of the cyc losome, Thus, MAD2 links the mitotic checkpoint pathway to the cyclin B destruction machinery which is critical in controlling the metaphase -anaphase transition.