Genetic Analysis of the Spindle Checkpoint Genes san-1, mdf-2, bub-3 and the CENP-F Homologues hcp-1 and hcp-2 in Caenorhabditis Elegans


Show simple item record Hajeri, Vinita A en_US Stewart, Anil M en_US Moore, Landon L en_US Padilla, Pamela A en_US 2011-12-30T00:07:01Z 2011-12-30T00:07:01Z 2008 en_US 2008-2-4 en_US
dc.identifier.citation Hajeri, Vinita A, Anil M Stewart, Landon L Moore, Pamela A Padilla. "Genetic analysis of the spindle checkpoint genes san-1, mdf-2, bub-3 and the CENP-F homologues hcp-1 and hcp-2 in Caenorhabditis elegans" Cell Division 3:6. (2008) en_US
dc.identifier.issn 1747-1028 en_US
dc.description.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. en_US
dc.description.sponsorship National Institutes of Health; National Institute of General Medicine Sciences (R01 GM069419) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2008 Hajeri et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution 2.0 License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri en_US
dc.title Genetic Analysis of the Spindle Checkpoint Genes san-1, mdf-2, bub-3 and the CENP-F Homologues hcp-1 and hcp-2 in Caenorhabditis Elegans en_US
dc.type article en_US
dc.identifier.doi 10.1186/1747-1028-3-6 en_US
dc.identifier.pubmedid 18248670 en_US
dc.identifier.pmcid 2265278 en_US

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