Genetic Analysis of the Mitotic Spindle

Hoyt, M. Andrew; Geiser, John R.

doi:10.1146/annurev.genet.30.1.7

Cited by 83 publications

(70 citation statements)

References 163 publications

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“…Initially, seven proteins were identified as SAC components in yeast (i.e. Bub1-3, Mad1-3, and Mps1) (Hoyt and Geiser, 1996;Rudner and Murray, 1996;Weiss and Winey, 1996); additional factors such as CENP-E, ZW10, Rod and Rae1 (Abrieu et al, 2000;Basto et al, 2000;Babu et al, 2003) were later proposed for metazoan SAC. The importance of SAC in normal cellular metabolism is reflected in its frequent dysfunction in human cancers (Draviam et al, 2004;Lengauer and Wang, 2004), and in its role for dictating cellular responsiveness to chemotherapeutic agents Vogel et al, 2005).…”

Section: à10mentioning

confidence: 99%

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

et al. 2005

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The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage.

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Section: à10mentioning

confidence: 99%

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

et al. 2005

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“…It is now established that the formation and function of the mitotic spindle requires numerous microtubule (MT)-based motor proteins (Hoyt and Geiser, 1996;Vale and Fletterick, 1997). Although the identities of many of these mitotic motors are becoming clear, their specific functional interrelationships have been extremely difficult to ascertain.…”

Section: Introductionmentioning

confidence: 99%

Functional Coordination of Three Mitotic Motors inDrosophilaEmbryos

Sharp

Brown

Kwon

et al. 2000

MBoC

217

293

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It is well established that multiple microtubule-based motors contribute to the formation and function of the mitotic spindle, but how the activities of these motors interrelate remains unclear.Here we visualize spindle formation in living Drosophila embryos to show that spindle pole movements are directed by a temporally coordinated balance of forces generated by three mitotic motors, cytoplasmic dynein, KLP61F, and Ncd. Specifically, our findings suggest that dynein acts to move the poles apart throughout mitosis and that this activity is augmented by KLP61F after the fenestration of the nuclear envelope, a process analogous to nuclear envelope breakdown, which occurs at the onset of prometaphase. Conversely, we find that Ncd generates forces that pull the poles together between interphase and metaphase, antagonizing the activity of both dynein and KLP61F and serving as a brake for spindle assembly. During anaphase, however, Ncd appears to have no effect on spindle pole movements, suggesting that its activity is downregulated at this time, allowing dynein and KLP61F to drive spindle elongation during anaphase B. INTRODUCTIONThe segregation of chromosomes during mitosis depends on the action of a self-organizing, bipolar machine called the mitotic spindle. It is now established that the formation and function of the mitotic spindle requires numerous microtubule (MT)-based motor proteins (Hoyt and Geiser, 1996;Vale and Fletterick, 1997). Although the identities of many of these mitotic motors are becoming clear, their specific functional interrelationships have been extremely difficult to ascertain.Among all mitotic movements, the positioning of spindle poles during the assembly and elongation of the bipolar mitotic spindle may require the greatest degree of cooperation between different motors. This process is particularly complex because it occurs in a pathway consisting of several, temporally distinct stages, during which the organization of spindle microtubules and the general environment of the cell change dramatically (McIntosh and McDonald, 1989). The members of at least three families of MT motors are thought to play important roles in this pathway. These are the bipolar kinesins, the C-terminal kinesins, and cytoplasmic dynein.The bipolar (or BimC) kinesins (Vale and Fletterick, 1997) comprise a family of plus-end-directed motors, which have a bipolar morphology with motor domains at both ends of a central rod (Cole et al., 1994; Kashina et al., 1996a,b; Gordon and Roof, 2000). Functionally, these motors are thought to play a role in either the assembly or maintenance of spindle bipolarity, because their inhibition results in the formation of monopolar mitotic spindles (Enos and Morris, 1990;Hagan and Yanagida, 1990;Roof et al., 1991;Hoyt et al., 1992;Sawin et al., 1992;Heck et al., 1993;Blangy et al., 1995;Sharp et al., 1999b). Support for a role for bipolar kinesins in spindle maintenance but not assembly comes from the recent findings that inhibiting the Drosophila bipolar kinesin KLP61F does not pr...

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“…Both aspects of spindle development are regulated by the spindle pole body (SPB; the yeast microtubule-organizing center). SPBs organize cytoplasmic and intranuclear microtubules throughout the cell cycle (Byers and Goetsch, 1975;Hoyt and Geiser, 1996). As cells progress through the G1/S transition, the SPB is duplicated (Byers, 1981;Lew et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

Bud6 Directs Sequential Microtubule Interactions with the Bud Tip and Bud Neck during Spindle Morphogenesis inSaccharomyces cerevisiae

Segal

Bloom

Reed

2000

MBoC

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In budding yeast, spindle polarity relies on a precise temporal program of cytoplasmic microtubule-cortex interactions throughout spindle assembly. Loss of Clb5-dependent kinase activity under conditions of attenuated Cdc28 function disrupts this program, resulting in diploid-specific lethality. Here we show that polarity loss is tolerated by haploids due to a more prominent contribution of microtubule-neck interactions to spindle orientation inherent to haploids. These differences are mediated by the relative partition of Bud6 between the bud tip and bud neck, distinguishing haploids from diploids. Bud6 localizes initially to the bud tip and accumulates at the neck concomitant with spindle assembly. bud6⌬ mutant phenotypes are consistent with Bud6's role as a cortical cue for cytoplasmic microtubule capture. Moreover, mutations that affect Bud6 localization and partitioning disrupt the sequential program of microtubule-cortex interactions accordingly. These data support a model whereby Bud6 sequentially cues microtubule capture events at the bud tip followed by capture events at the bud neck, necessary for correct spindle morphogenesis and polarity.

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Genetic Analysis of the Mitotic Spindle

Cited by 83 publications

References 163 publications

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint

Functional Coordination of Three Mitotic Motors inDrosophilaEmbryos

Bud6 Directs Sequential Microtubule Interactions with the Bud Tip and Bud Neck during Spindle Morphogenesis inSaccharomyces cerevisiae

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