Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formation

Gestaut, Daniel R.; Graczyk, Beth; Cooper, Jeremy; Widlund, Per O.; Zelter, Alex; Wordeman, Linda; Asbury, Charles L.; Davis, Trisha N.

doi:10.1038/ncb1702

Cited by 145 publications

(228 citation statements)

References 35 publications

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“…7). This model is supported by recent in vitro studies showing that phosphorylation of a key kinetochore protein complex (Dam1) by Ipl1 reduces either its affinity for microtubules (8) or its association with the Ndc80 complex (9, 10), another key kinetochore complex.…”

supporting

confidence: 61%

Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase

Tatchell

Makrantoni

Stark

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Ipl1/Aurora B is the catalytic subunit of a complex that is required for chromosome segregation and nuclear division. Before anaphase, Ipl1 localizes to kinetochores, where it is required to establish proper kinetochore-microtubule associations and regulate the spindle assembly checkpoint. The protein phosphatase Glc7/ PP1 opposes Ipl1 for some of these activities. To more thoroughly characterize the Glc7 phosphatase that opposes Ipl1, we have identified mutations that suppress the thermosensitivity of an ipl1-2 mutant. In addition to mutations in genes previously associated with ipl1 suppression, we recovered a null mutant in TCO89, which encodes a subunit of the TOR complex 1 (TORC1), the conserved rapamycin-sensitive kinase activity that regulates cell growth in response to nutritional status. The temperature sensitivity of ipl1-2 can also be suppressed by null mutation of TOR1 or by administration of pharmacological TORC1 inhibitors, indicating that reduced TORC1 activity is responsible for the suppression. Suppression of the ipl1-2 growth defect is accompanied by increased fidelity of chromosome segregation and increased phosphorylation of the Ipl1 substrates histone H3 and Dam1. Nuclear Glc7 levels are reduced in a tco89 mutant, suggesting that TORC1 activity is required for the nuclear accumulation of Glc7. In addition, several mutant GLC7 alleles that suppress the temperature sensitivity of ipl1-2 exhibit negative synthetic genetic interactions with TORC1 mutants. Together, our results suggest that TORC1 positively regulates the Glc7 activity that opposes Ipl1 and provide a mechanism to tie nutritional status with mitotic regulation.

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supporting

confidence: 61%

Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase

Tatchell

Makrantoni

Stark

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…Together, these findings show that in fission yeast, Dam1 forms small speckles both on cytoplasmic MTs during interphase and kinetochores during mitosis. Similar small assemblies, called patches, also formed in vitro with recombinant ScDam1 complex (10,15,16). Hereafter, we refer to the small SpDam1 speckles as patches.…”

Section: Identification Of Discrete Dam1 Assemblies On Cytoplasmic Mtmentioning

confidence: 99%

“…With less than 16 copies of Dam1 complex per oligomer (one to four copies by one account) (15), the small assemblies, called patches, are nonetheless able to oscillate along the MT and track the depolymerizing end of a MT (15,16). Mechanistically, the power-stroke model cannot adequately explain how these small Dam1 oligomers, without an encircling structure to secure the topological association with the MT, are able to track the dynamic end of a shortening MT.…”

mentioning

confidence: 99%

“…Mechanistically, the power-stroke model cannot adequately explain how these small Dam1 oligomers, without an encircling structure to secure the topological association with the MT, are able to track the dynamic end of a shortening MT. Instead, the alternative "biased diffusion" model may provide a satisfactory explanation (12,15,17). This model postulates that the direction of Dam1 diffusion at the MT end is highly biased inwards along the MT to lower the free energy, effectively resulting in MT end-tracking movement instead of dissociation.…”

mentioning

confidence: 99%

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A non-ring-like form of the Dam1 complex modulates microtubule dynamics in fission yeast

Gao

Courthéoux

Gachet

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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The Dam1 complex is a kinetochore component that couples chromosomes to the dynamic ends of kinetochore microtubules (kMTs). Work in the budding yeast Saccharomyces cerevisiae has shown that the Dam1 complex forms a 16-unit ring encircling and tracking the tip of a MT in vitro, consistent with its cellular function as a coupler. Dam1 also forms smaller, nonring patches in vitro that track the dynamic ends of MTs. However, the identity of Dam1’s functional form in vivo remains unknown. Here we report a comprehensive in vivo characterization of Dam1 in the fission yeast Schizosaccharomyces pombe . In addition to their dense localizations on kinetochores and spindle MTs during mitosis, we identify that Dam1 is also localized onto cytoplasmic MTs as discrete spots in interphase, providing the unique opportunity to analyze Dam1 oligomers at the single-particle resolution in live cells. Such analysis shows that each oligomer contains one to five copies of Dam1, and is able to “switch-rail” while moving along MTs, precluding the possibility of a 16-unit encircling structure. Dam1 patches track the plus ends of the shortening, but not the elongating, MTs and retard MT depolymerization. Together with Mal3, the EB1-like MT-interacting protein, cytoplasmic Dam1 plays an important role in maintaining proper cell shape. In mitosis, kinetochore-associated Dam1 appears to facilitate kMT depolymerization. Together, our findings suggest that patches, instead of rings, are the physiologically functional forms of Dam1 in pombe. Our findings help establish the benchmark parameters of the Dam1 coupler and elucidate the mechanism of its functions.

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“…Additionally, it was subsequently shown that ring formation is not required for microtubule depolymerization-driven motion of the Dam1 complex [133,134].…”

Section: Force Generation By Microtubule Depolymerization From Plus-endsmentioning

confidence: 99%

The perpetual movements of anaphase

Maiato

Lince-Faria

2010

Cell. Mol. Life Sci.

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One of the most extraordinary events in the lifetime of a cell is the coordinated separation of sister chromatids during cell division. This is truly the essence of the entire mitotic process and the reason for the most profound morphological changes in cytoskeleton and nuclear organization that a cell may ever experience. It all occurs within a very short time window known as "anaphase", as if the cell had spent the rest of its existence getting ready for this moment in an ultimate act of survival. And there is a good reason for this: no space for mistakes. Problems in the distribution of chromosomes during cell division have been correlated with aneuploidy, a common feature observed in cancers and several birth defects, and the main cause of spontaneous abortion in humans. In this paper we critically review the mechanisms of anaphase chromosome motion that resisted the scrutiny of more than one hundred years of research as part of a tribute to the pioneering work of Miguel Mota.

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Phosphoregulation and depolymerization-driven movement of the Dam1 complex do not require ring formation

Cited by 145 publications

References 35 publications

Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase

Temperature-sensitive ipl1-2/Aurora B mutation is suppressed by mutations in TOR complex 1 via the Glc7/PP1 phosphatase

A non-ring-like form of the Dam1 complex modulates microtubule dynamics in fission yeast

The perpetual movements of anaphase

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