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.
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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DOI：
10.1186/1747-1028-3-6
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发表时间：
2008-02-04
期刊：
影响因子：
2.3
通讯作者：
Padilla PA
中科院分区：
文献类型：
--
作者：
Hajeri VA;Stewart AM;Moore LL;Padilla PA
纺锤体检查点延迟后期的开始，直到所有姐妹染色单体在中期板上正确对齐。为了研究MAD 3同源物san-1在秀丽隐杆线虫胚胎中的作用，我们使用RNA干扰（RNAi）来鉴定具有活san-1（ok 1580）缺失突变体的合成致死基因。san-1（ok 1580）动物具有低穿透表型，包括雄性发生率增加、幼虫停滞、生长缓慢、外阴突出和外阴形态发生缺陷。我们发现，当HCP-1（CENP-F同源物）、MDF-1（MAD-1同源物）、MDF-2（MAD-2同源物）或BUB-3（预测的BUB-3同源物）被RNA干扰减少时，san-1（ok 1580）胚胎的生存力显着降低。有趣的是，当HCP-1，HCP-2的比例降低时，san-1（ok 1580）胚胎的存活率并没有显著降低。san-1（ok 1580）;hcp-1（RNAi）胚胎的表型包括胚胎和幼虫致死率、异常器官发育和异常染色体分离增加（异常有丝分裂核、后期桥接）。几只san-1（ok 1580）;hcp-1（RNAi）动物显示出异常的动粒（通过MPM-2检测）和微管结构。mdf-2（RNAi）;hcp-1（RNAi）胚胎的存活也受到损害，但bub-3（RNAi）;hcp-1（RNAi）胚胎没有。最后，我们发现san-1（ok 1580）和bub-3（RNAi），而不是hcp-1（RNAi）胚胎，对缺氧敏感，这表明像SAN-1，BUB-3具有作为纺锤体检查点蛋白的功能作用。总之，这些数据表明，在C。在线虫胚胎中，HCP-1与纺锤体检查点途径的一个子集相互作用。此外，san-1（ok 1580）;hcp-1（RNAi）动物具有严重的活力缺陷，而在san-1（ok 1580）;hcp-2（RNAi）和san-1（ok 1580）;hcp-2（ok 1757）动物中，活力缺陷不那么严重，这表明hcp-1和hcp-2不是完全多余的。
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. 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. 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.
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DOI：
10.1083/jcb.153.6.1209
发表时间：
2001-06-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Oegema K;Desai A;Rybina S;Kirkham M;Hyman AA
通讯作者：
Hyman AA
影响因子：
21.3
作者：
Kitagawa, R;Rose, AM
通讯作者：
Rose, AM
影响因子：
4
作者：
Amon, A
通讯作者：
Amon, A
DOI：
10.1073/pnas.80.10.2926
发表时间：
1983-01-01
期刊：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES
影响因子：
--
作者：
DAVIS, FM;TSAO, TY;RAO, PN
通讯作者：
RAO, PN
影响因子：
3.3
作者：
Encalada, SE;Willis, J;Bowerman, B
通讯作者：
Bowerman, B