UNLABELLED: ABSTRACT: BACKGROUND: The spindle checkpoint delays the onset of anaphase until all sister chromatids are aligned properly at the metaphase plate. To investigate the role
san-1, the MAD3 homologue, has in Caenorhabditis elegans embryos we used RNA interference (RNAi) to identify genes synthetic lethal with the viable
san-1(
ok1580) deletion mutant. RESULTS: The
san-1(
ok1580) animal has low penetrating phenotypes including an increased incidence of males, larvae arrest, slow growth, protruding vulva, and defects in vulva morphogenesis. We found that the viability of
san-1(
ok1580) embryos is significantly reduced when HCP-1 (CENP-F homologue), MDF-1 (MAD-1 homologue), MDF-2 (MAD-2 homologue) or BUB-3 (predicted BUB-3 homologue) are reduced by RNAi. Interestingly, the viability of
san-1(
ok1580) embryos is not significantly reduced when the paralog of HCP-1, HCP-2, is reduced. The phenotype of
san-1(
ok1580);
hcp-1(RNAi) embryos includes embryonic and larval lethality, abnormal organ development, and an increase in abnormal chromosome segregation (aberrant mitotic nuclei, anaphase bridging). Several of the
san-1(
ok1580);
hcp-1(RNAi) animals displayed abnormal kinetochore (detected by MPM-2) and microtubule structure. The survival of
mdf-2(RNAi);
hcp-1(RNAi) embryos but not
bub-3(RNAi);
hcp-1(RNAi) embryos was also compromised. Finally, we found that
san-1(
ok1580) and
bub-3(RNAi), but not
hcp-1(RNAi) embryos, were sensitive to anoxia, suggesting that like SAN-1, BUB-3 has a functional role as a spindle checkpoint protein. CONCLUSION: Together, these data suggest that in the C. elegans embryo, HCP-1 interacts with a subset of the spindle checkpoint pathway. Furthermore, the fact that
san-1(
ok1580);
hcp-1(RNAi) animals had a severe viability defect whereas in the
san-1(
ok1580);
hcp-2(RNAi) and
san-1(
ok1580);
hcp-2(
ok1757) animals the viability defect was not as severe suggesting that
hcp-1 and
hcp-2 are not completely redundant.