A role for the DNA-damage checkpoint kinase Chk1 in the virulence program of the fungus<i>Ustilago maydis</i>

Mielnichuk, Natalia; Sgarlata, Cecilia; Pérez-Martı́n, José

doi:10.1242/jcs.052233

Cited by 31 publications

(72 citation statements)

References 40 publications

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“…Any condition resulting in inhibition of Cdk1-Clb2 complex produces both a G2 delay/arrest as well as the induction of strong polar growth. These conditions include mutations affecting either the Cdk1-Clb2 complex directly (García-Muse et al., 2004); the balance of inhibitory phosphorylation via Wee1 or Cdc25 activities (Sgarlata and Pérez-Martín, 2005a;Sgarlata and Pérez-Martín, 2005b); the response to checkpoint activation such as the DNA damage response (Pérez-Martín, 2009); or the response to developmental cues, such as the virulence program (Mielnichuk et al, 2009). We observed that conditional removal of wee1 or expression of a cdk1 allele refractory to inhibitory phosphorylation prevented the hyperpolar growth observed in ukc1 mutants.…”

Section: Discussionmentioning

confidence: 63%

“…Different signaling cascades seem to converge on the regulation of Cdk1 inhibitory phosphorylation in U. maydis. These cascades include the b-dependent pathogenic program (de Sena-Tomás et al, 2011;Mielnichuk et al, 2009), DNA damage response (Mielnichuk and Pérez-Martín, 2008;Pérez-Martín, 2009), the Cell Wall Integrity pathway (Carbo and Pérez-Martín, 2010) and the pheromone response pathway (S. Castanheira and J.P.-M., unpublished data). In general cell cycle has been considered as a final effector, which is accordingly modified upon previous integration of the various signaling cascades in the cell.…”

Section: Discussionmentioning

confidence: 99%

“…Bud formation takes place during G2 phase and relies almost entirely on polar growth (Steinberg et al, 2001). Therefore, any condition resulting in a G2 cell cycle delay or arrest in U. maydis also correlates with a strong polar growth (Mielnichuk et al, 2009;Pérez-Martín, 2009;Pérez-Martín and Castillo-Lluva, 2008). Although the details are largely unknown, it is likely that several elements could be involved in the communication between cell cycle and polar growth during G2 phase in U. maydis.…”

Section: Hyperpolar Growth In Mor-defective Cells Depends On Wee1 Kinasementioning

confidence: 99%

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The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

Sartorel

Pérez-Martı́n

2012

Journal of Cell Science

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SummaryThe morphogenesis-related NDR kinase (MOR) pathway regulates morphogenesis in fungi. In spite of the high conservation of its components, impairing their functions results in highly divergent cellular responses depending on the fungal species. The reasons for such differences are unclear. Here we propose that the species-specific connections between cell cycle regulation and the MOR pathway could be partly responsible for these divergences. We based our conclusion on the characterization of the MOR pathway in the fungus Ustilago maydis. Each gene that encodes proteins of this pathway in U. maydis was deleted. All mutants exhibited a constitutive hyperpolarized growth, contrasting with the loss of polarity observed in other fungi. Using a conditional allele of the central NDR kinase Ukc1, we found that impairing MOR function resulted in a prolonged G2 phase. This cell cycle delay appears to be the consequence of an increase in Cdk1 inhibitory phosphorylation. Strikingly, prevention of the inhibitory Cdk1 phosphorylation abolished the hyperpolarized growth associated with MOR pathway depletion. We found that the prolonged G2 phase resulted in higher levels of expression of crk1, a conserved kinase that promotes polar growth in U. maydis. Deletion of crk1 also abolished the dramatic activation of polar growth in cells lacking the MOR pathway. Taken together, our results suggest that Cdk1 inhibitory phosphorylation may act as an integrator of signaling cascades regulating fungal morphogenesis and that the distinct morphological response observed in U. maydis upon impairment of the MOR pathway could be due to a cell cycle deregulation.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Hyperpolar Growth In Mor-defective Cells Depends On Wee1 Kinasementioning

confidence: 99%

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The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

Sartorel

Pérez-Martı́n

2012

Journal of Cell Science

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“…Previous research from our group has shown that efficient cell cycle arrest during the infective filament formation requires the cooperation of elements from the DNA damage response (DDR) cascade, such as the kinase Chk1 and its upstream activating kinase Atr1 (de Sena-Tomas et al, 2011;Mielnichuk et al, 2009;PerezMartin, 2009). During the early stages of formation of the infective hypha, the Chk1 kinase is activated for a short period of time, resulting in a transient G2 cell cycle arrest (Mielnichuk et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Programmed cell cycle arrest is required for infection of corn plants by the fungus Ustilago maydis

2014

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Ustilago maydis is a plant pathogen that requires a specific structure called infective filament to penetrate the plant tissue. Although able to grow, this filament is cell cycle arrested on the plant surface. This cell cycle arrest is released once the filament penetrates the plant tissue. The reasons and mechanisms for this cell cycle arrest are unknown. Here, we have tried to address these questions. We reached three conclusions from our studies. First, the observed cell cycle arrest is the result of the cooperation of at least two distinct mechanisms: one involving the activation of the DNA damage response (DDR) cascade; and the other relying on the transcriptional downregulation of Hsl1, a kinase that modulates the G2/M transition. Second, a sustained cell cycle arrest during the infective filament step is necessary for the virulence in U. maydis, as a strain unable to arrest the cell cycle was severely impaired in its ability to infect corn plants. Third, production of the appressorium, a structure required for plant penetration, is incompatible with an active cell cycle. The inability to infect plants by strains defective in cell cycle arrest seems to be caused by their failure to induce the appressorium formation process. In summary, our findings uncover genetic circuits to arrest the cell cycle during the growth of this fungus on the plant surface, thus allowing the penetration into plant tissue.

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“…These kinases are broadly conserved regulators (Abraham 2001;Bartek and Lukas 2003). Recent work performed in the phytopathogenic basidiomycete Ustilago maydis (Mielnichuk et al 2009;de Sena-Tomas et al 2011;Perez-Martin and de Sena-Tomas 2011) suggested a role for the kinases Atr1 and Chk1 in the regulation of the dikaryotic cell cycle. U. maydis cells defective in these kinases showed impaired dikaryon proliferation.…”

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confidence: 99%

A DNA Damage Checkpoint Pathway Coordinates the Division of Dikaryotic Cells in the Ink Cap MushroomCoprinopsis cinerea

et al. 2013

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The fungal fruiting body or mushroom is a multicellular structure essential for sexual reproduction. It is composed of dikaryotic cells that contain one haploid nucleus from each mating partner sharing the same cytoplasm without undergoing nuclear fusion. In the mushroom, the pileus bears the hymenium, a layer of cells that includes the specialized basidia in which nuclear fusion, meiosis, and sporulation occur. Coprinopsis cinerea is a well-known model fungus used to study developmental processes associated with the formation of the fruiting body. Here we describe that knocking down the expression of Atr1 and Chk1, two kinases shown to be involved in the response to DNA damage in a number of eukaryotic organisms, dramatically impairs the ability to develop fruiting bodies in C. cinerea, as well as other developmental decisions such as sclerotia formation. These developmental defects correlated with the impairment in silenced strains to sustain an appropriated dikaryotic cell cycle. Dikaryotic cells in which chk1 or atr1 genes were silenced displayed a higher level of asynchronous mitosis and as a consequence aberrant cells carrying an unbalanced dose of nuclei. Since fruiting body initiation is dependent on the balanced mating-type regulator doses present in the dikaryon, we believe that the observed developmental defects were a consequence of the impaired cell cycle in the dikaryon. Our results suggest a connection between the DNA damage response cascade, cell cycle regulation, and developmental processes in this fungus. IN fungal cells, mating-the process equivalent to fertilizationbrings together two haploid nuclei in the same cytoplasm. It is generally thought that this process is essentially followed by nuclear fusion, resulting in a diploid nucleus that either enters meiosis immediately (as occurs in the fission yeast Schizosaccharomyces pombe) or is maintained and proliferates in the diploid state (as happens in the budding yeast Saccharomyces cerevisiae). However, in a large number of fungi, mating does not result in diploid nuclei. Instead, they form dikaryons, cells that contain one haploid nucleus from each mating partner sharing the same cytoplasm for a period of time without undergoing nuclear fusion or meiosis. These dikaryons continue to propagate, and eventually nuclear fusion will take place, which will be followed by meiosis, closing the sexual cycle (Brown and Casselton 2001).Dikaryon cell division, also called conjugate division, represents a big challenge to the cell since it has to ensure that each daughter dikaryon inherits a balance of each parental genome. For that, a complex cell cycle is required that involves distinct mechanisms to maintain heterokaryosis after cell division. For example, for a large number of Basidiomycota (e.g., the mushroom Coprinopsis cinerea), conjugate division includes the formation of a structure known as the clamp connection or clamp cell, as well as the sorting of one of the nuclei to this structure (Casselton 1978;Brown and Casselton 2001). In the...

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A role for the DNA-damage checkpoint kinase Chk1 in the virulence program of the fungusUstilago maydis

Cited by 31 publications

References 40 publications

The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

The distinct wiring between cell cycle regulation and the widely conserved Morphogenesis-Related (MOR) pathway in the fungus Ustilago maydis determines the morphological outcome

Programmed cell cycle arrest is required for infection of corn plants by the fungus Ustilago maydis

A DNA Damage Checkpoint Pathway Coordinates the Division of Dikaryotic Cells in the Ink Cap MushroomCoprinopsis cinerea

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