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

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dc.contributor.author Hajeri, Vinita A en_US
dc.contributor.author Stewart, Anil M en_US
dc.contributor.author Moore, Landon L en_US
dc.contributor.author Padilla, Pamela A en_US
dc.date.accessioned 2011-12-30T00:07:01Z
dc.date.available 2011-12-30T00:07:01Z
dc.date.copyright 2008 en_US
dc.date.issued 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.identifier.uri http://hdl.handle.net/2144/2682
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 (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 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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