Triggering the all-or-nothing switch into mitosis

O’Farrell, Patrick H.

doi:10.1016/s0962-8924(01)02142-0

Cited by 168 publications

(154 citation statements)

References 58 publications

(59 reference statements)

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“…The list of proteins that could be responsible for this phenotype is not exhaustive, and could be limited to a factor involved in the Toxoplasma mitotic checkpoint. Yeast strains deficient in the cyclinB/cdk pathway have also been shown to arrest in G1 and mitosis (van der Velden and Lohka, 1993;Clute and Pines, 1999;D'Angiolella et al, 2001;O'Farrell, 2001) which reflects the dual action of this cyclin class on START and mitotic checkpoints (Hartwell, 1991;O'Farrell, 2001). Rescue of the defect in ts11C9 with a homologue of eukaryotic XPCM2 is also consistent with a defect involving the mitotic cyclin pathway.…”

Section: Discussionmentioning

confidence: 90%

“…The DNA content of asynchronously growing TgXPMC2-tr11C9 parasites was also unaffected by temperature ( Fig. 4B and C, filled histogram) and was indistinguishable from RHDhxgprt parasite profiles (data not shown) (Radke et al, 2000;2001) whereas ts11C9 DNA profiles (bold trace overlay) displayed the characteristic bimodal 1 N and 2 N distributions when shifted to 40∞C (Fig. 4C).…”

Section: Cell Cycle Analysis Of Tgxpmc2 Transformantsmentioning

confidence: 91%

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Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

White

Jerome

Vaishnava

et al. 2005

Molecular Microbiology

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SummaryGrowth rate is a major pathogenesis factor in the parasite Toxoplasma gondii ; however, how cell division is controlled in this protozoan is poorly understood. Herein, we show that centrosomal duplication is an indicator of S phase entry while centrosome migration marks mitotic entry. Using the pattern of centrosomal replication, we confirmed that mutant ts 11C9 undergoes a bimodal cell cycle arrest that is characterized by two subpopulations containing either single or duplicated centrosomes which correlate with the bipartite genome distribution observed at the non-permissive temperature. Genetic rescue of ts 11C9 was performed using a parental RH strain cDNA library, and the cDNA responsible for conferring temperature resistance (growth at 40 ∞ ∞ ∞ ∞ C) was recovered by recombination cloning. A single T. gondii gene encoding the protein homologue of XPMC2 was responsible for genetic rescue of the temperature-sensitive defect in ts 11C9 parasites. This protein is a known suppressor of mitotic defects, and in tachyzoites, TgXPMC2-YFP localized to the parasite nucleus and nucleolus which is consistent with the expected subcellular localization of critical mitotic factors. Altogether, these results demonstrate that ts 11C9 is a conditional mitotic mutant containing a single defect which influences two distinct control points in the T. gondii tachyzoite cell cycle.

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Section: Discussionmentioning

confidence: 90%

Section: Cell Cycle Analysis Of Tgxpmc2 Transformantsmentioning

confidence: 91%

Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

White

Jerome

Vaishnava

et al. 2005

Molecular Microbiology

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“…Mitosis is regulated by cell cycle-specific phosphorylation and regulated proteolysis of regulatory proteins mediated by activation and inactivation of cyclin-dependent kinases (CDKs) (O'Farrell, 2001) in all eukaryotes, including Aspergillus nidulans . In A. nidulans, mitosis is also regulated by a second kinase, NIMA (never in mitosis A), which when inactivated arrests cell in G 2 even though the CDK1 complex is active (Osmani et al, 1991a).…”

Section: Introductionmentioning

confidence: 99%

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

Osmani

Davies

Oakley

et al. 2003

MBoC

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The tinA gene of Aspergillus nidulans encodes a protein that interacts with the NIMA mitotic protein kinase in a cell cycle-specific manner. Highly similar proteins are encoded in Neurospora crassa and Aspergillus fumigatus. TINA and NIMA preferentially interact in interphase and larger forms of TINA are generated during mitosis. Localization studies indicate that TINA is specifically localized to the spindle pole bodies only during mitosis in a microtubule-dependent manner. Deletion of tinA alone is not lethal but displays synthetic lethality in combination with the anaphase-promoting complex/cyclosome mutation bimE7. At the bimE7 metaphase arrest point, lack of TINA enhanced the nucleation of bundles of cytoplasmic microtubules from the spindle pole bodies. These microtubules interacted to form spindles joined in series via astral microtubules as revealed by live cell imaging. Because TINA is modified and localizes to the spindle pole bodies at mitosis, and lack of TINA causes enhanced production of cytoplasmic microtubules at metaphase arrest, we suggest TINA is involved in negative regulation of the astral microtubule organizing capacity of the spindle pole bodies during metaphase. INTRODUCTIONMitosis is regulated by cell cycle-specific phosphorylation and regulated proteolysis of regulatory proteins mediated by activation and inactivation of cyclin-dependent kinases (CDKs) (O'Farrell, 2001) in all eukaryotes, including Aspergillus nidulans . In A. nidulans, mitosis is also regulated by a second kinase, NIMA (never in mitosis A), which when inactivated arrests cell in G 2 even though the CDK1 complex is active (Osmani et al., 1991a). Without activation of NIMA, active CDK1 is unable to accumulate in the nucleus but does so after mutation of the nuclear pore complex protein SONA rae1/gle2 (Wu et al., 1998). NIMA may therefore interact with the nuclear pore complex to help mediate localization of CDK1 at mitosis.NIMA is regulated at multiple levels, including mRNA abundance (Osmani et al., 1987), phosphorylation , and proteolysis Ye et al., 1998). NIMA has also been shown to have a dynamic localization during mitosis being sequentially located to DNA, the mitotic spindle, and the spindle pole body (SPB) (De Souza et al., 2000).Expression of NIMA promotes chromatin condensation (O'Connell et al., 1994) and transient formation of mitotic spindle-like structures (Osmani et al., 1988b). Stable versions of NIMA prevent normal exit from mitosis . The mitotic promoting activity of NIMA crosses species barriers from yeast to humans (Lu and Hunter, 1995a), indicating conserved NIMA substrates are involved in mitotic regulation.NIMA-related kinases have been isolated from Neurospora crassa and Schizosaccharomyces pombe (Krien et al., 1998), and the S. pombe NIMA-like kinase Fin1p is involved in mitotic regulation (Grallert and Hagan, 2002;Krien et al., 2002). NIMA-related kinases (NEKs) have also been identified in higher eukaryotes (Letwin et al., 1992;Schultz and Nigg, 1993;Lu and Hunter, 1995b;Chen et al., 1999;Tana...

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Section: Introductionmentioning

confidence: 99%

“…At the onset of mitosis, rapid MPF activation is favored by a positive feedback loop involving Cdc25 phosphatases, MPF itself, and Polo-like kinases. Degradation of Cyclin B at the metaphaseto-anaphase transition by the anaphase promoting complex (APC) destroys the MPF complex and causes exit from mitosis (reviewed in Nurse, 1990; Whitaker and Patel., 1990;Norbury and Nurse, 1992;Nigg, 1995;Morgan, 1997Morgan, , 1999Beckhelling and Ford, 1998;O'Farrell, 2001).Amphibian eggs have proved extremely useful for the study of MPF regulation. Cycles of Cyclin B accumulation and destruction sufficient to drive synchronous cell cycles in the absence of any other protein synthesis occur in both fertilized or activated eggs and in egg extracts (Murray and Kirschner, 1989;Hartley et al, 1996).…”

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confidence: 99%

Pre-M Phase-promoting Factor Associates with Annulate Lamellae inXenopusOocytes and Egg Extracts

Beckhelling

Chang

Chevalier

et al. 2003

MBoC

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We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates. INTRODUCTIONThe structural changes accompanying mitosis and meiosis are governed in almost all species by M phase-promoting factor (MPF) (Masui and Markert, 1971), a complex of Cyclin B and the kinase Cdc2 (reviewed in Nigg, 1995;Morgan, 1997). Direct and indirect targets for MPF include the nuclear envelope and lamina, chromatin proteins, and regulators of mitotic spindle formation (Moreno and Nurse, 1990;Norbury and Nurse, 1992). MPF activation requires the continuous synthesis and accumulation during interphase of Cyclin B, which binds Cdc2 to form inactive pre-MPF. Pre-MPF is maintained inactive by inhibitory phosphorylation on Cdc2 by the Wee1 and Myt1 kinases. At the onset of mitosis, rapid MPF activation is favored by a positive feedback loop involving Cdc25 phosphatases, MPF itself, and Polo-like kinases. Degradation of Cyclin B at the metaphaseto-anaphase transition by the anaphase promoting complex (APC) destroys the MPF complex and causes exit from mitosis (reviewed in Nurse, 1990; Whitaker and Patel., 1990;Norbury and Nurse, 1992;Nigg, 1995;Morgan, 1997Morgan, , 1999Beckhelling and Ford, 1998;O'Farrell, 2001).Amphibian eggs have proved extremely useful for the study of MPF regulation. Cycles of Cyclin B accumulation and destruction sufficient to drive synchronous cell cycles in the absence of any other protein synthesis occur in both fertilized or activated eggs and in egg extracts (Murray and Kirschner, 1989;Hartley et al., 1996). Although MPF activation cycles in amphibian oocytes and eggs can continue in the absence of nuclei and microtubules (Hara et al., 1980;Shinagawa, 1983;Gerhart et al., 1984;Newport and Kirschner, 1984;Kimelman et al., 1987;Shinagawa, 1992) both in manipulate...

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Triggering the all-or-nothing switch into mitosis

Cited by 168 publications

References 58 publications

Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

Genetic rescue of a Toxoplasma gondii conditional cell cycle mutant

TINA Interacts with the NIMA Kinase inAspergillus nidulansand Negatively Regulates Astral Microtubules during Metaphase Arrest

Pre-M Phase-promoting Factor Associates with Annulate Lamellae inXenopusOocytes and Egg Extracts

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