The decision to enter mitosis: feedback and redundancy in the mitotic entry network

Lindqvist, Arne; Rodríguez-Bravo, Verónica; Medema, René H.

doi:10.1083/jcb.200812045

Cited by 514 publications

(549 citation statements)

References 113 publications

(156 reference statements)

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“…This is consistent with studies in S. cerevisiae and human cells that have shown that the Set1 complex functions in the DNA damage response (Corda et al 1999;Faucher and Wellinger 2010). Moreover, partial CDK1 activity in A. nidulans also results in sensitivity to DNA damaging agents (data not shown), potentially due to a reduced efficiency in recovering from DNA damage-mediated G2-M checkpoint arrest (Van Vugt et al 2005;Karlsson-Rosenthal and Millar 2006;Lindqvist et al 2009). It is possible then that a combination of lack of Set1 complex function and partial CDK1 function results in an increased sensitivity to naturally occurring DNA damage in the absence of external agents of DNA damage, thus causing a G2 delay.…”

Section: Discussionsupporting

confidence: 78%

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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Mitosis is promoted and regulated by reversible protein phosphorylation catalyzed by the essential NIMA and CDK1 kinases in the model filamentous fungus Aspergillus nidulans. Protein methylation mediated by the Set1/COMPASS methyltransferase complex has also been shown to regulate mitosis in budding yeast with the Aurora mitotic kinase. We uncover a genetic interaction between An-swd1, which encodes a subunit of the Set1 protein methyltransferase complex, with NIMA as partial inactivation of nimA is poorly tolerated in the absence of swd1. This genetic interaction is additionally seen without the Set1 methyltransferase catalytic subunit. Importantly partial inactivation of NIMT, a mitotic activator of the CDK1 kinase, also causes lethality in the absence of Set1 function, revealing a functional relationship between the Set1 complex and two pivotal mitotic kinases. The main target for Set1-mediated methylation is histone H3K4. Mutational analysis of histone H3 revealed that modifying the H3K4 target residue of Set1 methyltransferase activity phenocopied the lethality seen when either NIMA or CDK1 are partially functional. We probed the mechanistic basis of these genetic interactions and find that the Set1 complex performs functions with CDK1 for initiating mitosis and with NIMA during progression through mitosis. The studies uncover a joint requirement for the Set1 methyltransferase complex with the CDK1 and NIMA kinases for successful mitosis. The findings extend the roles of the Set1 complex to include the initiation of mitosis with CDK1 and mitotic progression with NIMA in addition to its previously identified interactions with Aurora and type 1 phosphatase in budding yeast.D URING the transition from interphase into mitosis, chromatin undergoes dramatic global restructuring to go from a relaxed interphase configuration amenable to gene expression to a condensed form characteristic of mitotic chromosomes. Chromatin condensation not only marks mitosis but is also essential for the normal segregation of the duplicated sister chromatids into daughter nuclei. On the other hand, during mitotic exit, decondensation of chromatin needs to be triggered in a correct temporal manner to enable successful transition into interphase. In Aspergillus nidulans, a model filamentous fungus that enabled discovery of cell cycle-specific genes, mitotic initiation requires the function of the essential NIMA mitotic kinase (Oakley and Morris 1983;Osmani et al. 1987). Early evidence pointed to a role for NIMA in regulating chromatin compaction through the cell cycle since overexpression of NIMA was sufficient to induce chromatin condensation independent of cell cycle phase (Osmani et al. 1988;. Importantly, NIMA is required for, and can promote, the phosphorylation of histone H3 at serine 10 (De Souza et al. 2000), a universal marker of mitotic chromatin. In addition, NIMA has been shown to regulate the partial disassembly of nuclear pore complexes, allowing the access of mitotic regulators to the nucleus (Wu et al. 1998;De S...

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Section: Discussionsupporting

confidence: 78%

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

et al. 2014

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“…As cells proceed to the G2 phase, the level of Cyclin B1 rapidly increased in the mitotic phase. The decision of cells to either remain in the G2/M phase or go through G2 phase into mitosis requires the activation of Cdc2 protein (Lindqvist et al 2009) whose activity is regulated by synthesis of Cyclin B1 and subsequent complex formation. This complex formation is triggered by a 10-fold increase in Cyclin B1 expression in the G2 phase.…”

Section: Discussionmentioning

confidence: 99%

Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation

2013

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Genistein is an isoflavonic phyto-oestrogen contained in soya beans. It is thought to display anti-cancer effects. This study was designed to investigate its effect on human intestinal colon cancer Caco-2 cells. MTT assay, flow cytometric analysis and western blotting were used to investigate the effect of genistein on cell proliferation, cell cycle progression and protein alterations of selected cell cycle-related proteins in Caco-2 cells. Our results showed that genistein and daidzein significantly suppressed cell proliferation. Genistein treatment was demonstrated to modulate cell cycle distribution through accumulation of cells at G2/M phase, with a significant decreasing effect of Cyclin B1 and Serine/threonine-protein kinase 2 (Chk2) proteins expression. However, daidzein did not alter the cell cycle progression in Caco-2 cells. All these observation strongly indicate that genistein has anti-proliferative effect in human intestinal colon cancer Caco-2 cells through the downregulation of cell cycle check point proteins, Cyclin B1 and Chk2.

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“…It is therefore not surprising that these kinase complexes are targets of the DNA-damage checkpoint. In G2 phase, the DNA-damage-mediated arrest of cell-cycle progression requires direct inhibition of CDK1-cyclin B, the CDK-cyclin complex that is required for mitotic entry (Linqvist et al, 2009). The regulation of CDK activity is controlled largely by inhibitory phosphorylation of the CDK sub unit, which is carried out by the kinase Wee1.…”

mentioning

confidence: 99%

Checkpoint recovery after DNA damage: a rolling stop for CDKs

Duursma

Cimprich

2010

EMBO Reports

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The decision to enter mitosis: feedback and redundancy in the mitotic entry network

Cited by 514 publications

References 113 publications

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

The Set1/COMPASS Histone H3 Methyltransferase Helps Regulate Mitosis With the CDK1 and NIMA Mitotic Kinases in Aspergillus nidulans

Genistein-induced G2/M cell cycle arrest of human intestinal colon cancer Caco-2 cells is associated with Cyclin B1 and Chk2 down-regulation

Checkpoint recovery after DNA damage: a rolling stop for CDKs

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