In Caenorhabditis elegans,
cdc-25.1 loss-of-function mutants display a lack of germline proliferation. We found that the proliferation defect of
cdc-25.1 mutants was suppressed by
wee-1.3 RNAi. Further, among the seven cdk and seven cyclin homologs examined,
cdk-1 and
cyb-3 RNAi treatment caused the most severe germline proliferation defects in an
rrf-1 mutant background, which were similar to those of the
cdc-25.1 mutants. In addition, while RNAi of
cyd-1 and
cye-1 caused significant germline proliferation defects, RNAi of
cdk-2 and
cdk-4 did not. Compared with the number of germ nuclei in
wee-1.3(RNAi) worms, the number in
wee-1.3(RNAi);
cdk-1(RNAi) and
wee-1.3(RNAi);
cyb-3(RNAi) worms further decreased to the level of
cdk-1(RNAi) and
cyb-3(RNAi) worms, respectively, indicating that
cdk-1 and
cyb-3 are epistatic and function downstream of
cdc-25.1 and
wee-1.3 in the control of the cell cycle. BrdU labeling of adult worms showed that, while 100% of the wild-type germ nuclei in the mitotic region incorporated BrdU when labeled for more than 12 h at 20C, a small fraction of the
cdc-25.1 mutant germ nuclei failed to incorporate BrdU even when labeled for 68 h. These results indicate that CDC-25.1 is required for maintaining proper rate of germline mitotic cell cycle. We propose that CDC-25.1 regulates the rate of germline mitotic cell cycle by counteracting WEE-1.3 and by positively controlling CDK-1, which forms a complex primarily with CYB-3, but also possibly with CYD-1 and CYE-1.