OOCYTE ACTIVATION AND PASSAGE THROUGH THE METAPHASE ANAPHASE TRANSITION OF THE MEIOTIC CELL-CYCLE IS BLOCKED IN CLAMS BY INHIBITORS OF HMG-CAA REDUCTASE-ACTIVITY/

Cell cycle progression for postembryonic cells requires the activity o f 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), the enzyme which catalyzes the production of the isoprenoid precursor, mevalonate . In this study, we examine the requirements of HMG-R activity for cel l cycle progression during the meiotic and early mitotic divisions usi ng oocytes and dividing embryos from the surf clam, Spisula solidissim a. Using two different inhibitors of HMG-R, we find that the activity of this enzyme appears to be required at three distinct points of the cell cycle during meiosis. Depending on the stage at which these inhib itors are added to synchronous clam cultures, a reversible cell cycle block is triggered at the time of activation or at metaphase of either meiosis I or LI, whereas there is no block to the mitotic cell cycle. Inhibition of HMG-R activity in activated oocytes does not affect the transient activation of p42(MAPK) but results in a block at metaphase of meiosis I that is accompanied by the stabilization of cyclins A an d B and p34(cdc2) kinase activity. Our results suggest that metabolite s from the mevalonate biosynthetic pathway can act to influence the pr ocess of activation, as well as the events later in the cell cycle tha t lead to cyclin proteolysis and the exit from M phase during clam mei osis.