Overexpression of apc10(+) in fission yeast can suppress the temperature sensitivity of nuc2-663 mutant but not its sterility

One of the key cell cycle regulators, the anaphase promoting complex (APC) or cyclosome, plays a dual role during mitotic exit. By destroying anaphase inhibitors it promotes sister chromatid separation, and by destroying B-ty pe cyclins it promotes cytokinesis and removes the replication block. Under unfavorable growth conditions, most eukaryotic cells, including the fissio n yeast Schizosaccharomyces pombe, exit mitosis normally but are arrested i n G(1) and do not enter the S phase. In S. pombe, mutations in two APC/cycl osome subunits, nuc2-663 and apc10(ts), cause mitotic defects at 36 degrees C, and under nitrogen starvation at 25 degreesC they lead to inability of s topping in G(1) and hence to sterility. To gain more insight into the mecha nisms regulating APC/cyclosome activity during normal growth and under nitr ogen starvation, we screened a genomic library to identify high-copy suppre ssors of the temperature sensitivity of nuc2-663. Here we show that overexp ression of apc10(+) allows this strain to grow at 32 degreesC and rescues i t from sensitivity to the protease inhibitor N-tosyl-L-phenylalanine chloro methyl ketone at 25 degreesC. These observations are consistent with the pr oposed role for Apc10p as a positive regulator of the APC/cyclosome. Howeve r, apc10(+) does not suppress the sterility of nuc2-663 mutant cells, sugge sting that it plays a specific role in APC regulation (e.g., in substrate r ecognition) rather than in general APC activation.