Iron-responsive Transcription Factor Aft1 Interacts with Kinetochore Protein Iml3 and Promotes Pericentromeric Cohesin

Hamza, Akil; Baetz, Kristin

doi:10.1074/jbc.m111.319319

Cited by 17 publications

(20 citation statements)

References 54 publications

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“…Recent studies reveal that S. cerevisiae Aft-type transcription factor Aft1 plays an essential role in remodeling cellular metabolism in addition to iron homeostasis [21], [22], [52]. We have identified a novel Aft-type factor CaAft2 in C. albicans , and confirmed that CaAft2 is able to rescue S. cerevisiae aft1Δ mutant growth defects under iron-limited conditions [31].…”

Section: Discussionsupporting

confidence: 65%

Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans

Cheng

et al. 2013

PLoS ONE

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Morphological transition and iron metabolism are closely relevant to Candida albicans pathogenicity and virulence. In our previous study, we demonstrated that C. albicans Aft2 plays an important role in ferric reductase activity and virulence. Here, we further explored the roles of C. albicans Aft2 in numerous cellular processes. We found that C. albicans Aft2 exhibited an important role in iron metabolism through bi-directional regulation effects on iron-regulon expression. Deletion of AFT2 reduced cellular iron accumulation under iron-deficient conditions. Furthermore, both reactive oxygen species (ROS) generation and superoxide dismutase (SOD) activity were remarkably increased in the aft2Δ/Δ mutant, which were thought to be responsible for the defective responses to oxidative stress. However, we found that over-expression of C. albicans AFT2 under the regulation of the strong PGK1 promoter could not effectively rescue Saccharomyces cerevisiae aft1Δ mutant defects in some cellular processes, such as cell-wall assembly, ion homeostasis and alkaline resistance, suggesting a possibility that C. albicans Aft2 weakened its functional role of regulating some cellular metabolism during the evolutionary process. Interestingly, deletion of AFT2 in C. albicans increased cell surface hydrophobicity, cell flocculation and the ability of adhesion to polystyrene surfaces. In addition, our results also revealed that C. albicans Aft2 played a dual role in regulating hypha-specific genes under solid and liquid hyphal inducing conditions. Deletion of AFT2 caused an impaired invasive growth in solid medium, but an increased filamentous aggregation and growth in liquid conditions. Moreover, iron deficiency and environmental cues induced nuclear import of Aft2, providing additional evidence for the roles of Aft2 in transcriptional regulation.

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Section: Discussionsupporting

confidence: 65%

Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans

Cheng

et al. 2013

PLoS ONE

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“…Centromeric areas are vital for preserving genome integrity through their role in chromosome segregation. Aft1 has been reported in only a few yeast centromeres ( 46 ), it is known to interact with proteins of kinetochores ( 26 ) and its deletion affects chromosomal segregation and cell growth ( 47 ). Furthermore, DNA damage checkpoint proteins were found in centromeres in mammals (including Sc Rad9's partial homologue Brca1) as reviewed ( 48 ).…”

Section: Resultsmentioning

confidence: 99%

Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae

Andreadis

Nikolaou

Fragiadakis

et al. 2014

Nucleic Acids Research

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DNA damage response and repair proteins are centrally involved in genome maintenance pathways. Yet, little is known about their functional role under non-DNA damage-inducing conditions. Here we show that Rad9 checkpoint protein, known to mediate the damage signal from upstream to downstream essential kinases, interacts with Aft1 transcription factor in the budding yeast. Aft1 regulates iron homeostasis and is also involved in genome integrity having additional iron-independent functions. Using genome-wide expression and chromatin immunoprecipitation approaches, we found Rad9 to be recruited to 16% of the yeast genes, often related to cellular growth and metabolism, while affecting the transcription of ∼2% of the coding genome in the absence of exogenously induced DNA damage. Importantly, Rad9 is recruited to fragile genomic regions (transcriptionally active, GC rich, centromeres, meiotic recombination hotspots and retrotransposons) non-randomly and in an Aft1-dependent manner. Further analyses revealed substantial genome-wide parallels between Rad9 binding patterns to the genome and major activating histone marks, such as H3K36me, H3K79me and H3K4me. Thus, our findings suggest that Rad9 functions together with Aft1 on DNA damage-prone chromatin to facilitate genome surveillance, thereby ensuring rapid and effective response to possible DNA damage events.

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“…This null effect of M. pulcherrima on S. cerevisiae strain seems to be related to the mechanism of action of pulcherriminic acid. Indeed, the lack of antimicrobial activity on S. cerevisiae could be due to the presence of AFT1 trascriptional factors that increase the level of expression of iron regulon genes (Hamza and Baetz ; Holmes‐Hampton et al . ).…”

Section: Discussionmentioning

confidence: 99%

Antimicrobial activity ofMetschnikowia pulcherrimaon wine yeasts

2014

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Aims: In the present study, it was investigated the antagonistic behaviour of Metschnikowia pulcherrima, as biocontrol agent, against the main wine yeast species involved in the winemaking process. Methods and Results: Seven strains of M. pulcherrima were evaluated for the antimicrobial activity against 114 yeast strains belonging to Pichia, Candida, Hanseniaspora, Kluyveromyces, Saccharomycodes, Torulaspora, Brettanomyces and Saccharomyces genera. Results showed both different inter-generic and intrageneric responses to the antimicrobial action of M. pulcherrima strains. Interestingly, the antimicrobial activity of M. pulcherrima did not have any influence on the growth of Saccharomyces cerevisiae. Instead, M. pulcherrima displayed a broad and effective antimicrobial action on undesired wild spoilage yeasts, such as Brettanomyces/Dekkera, Hanseniaspora and Pichia genera. Fermentation trials carried out in synthetic grape must confirmed the antimicrobial activity of M. pulcherrima, determining the early death of the non-Saccharomyces co-inoculated cultures. Conclusions: The antimicrobial activity of M. pulcherrima does not seem due to proteinaceous compounds such as killer phenomenon, but to the pulcherriminic acid (the precursor of pulcherrimin pigment) that depletes iron present in the medium, making it not available to the other yeasts. Significance and Impact of the Study: These data agree with and further support the potential use of selected M. pulcherrima strains in controlled multistarter fermentations with S. cerevisiae starter cultures.

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Iron-responsive Transcription Factor Aft1 Interacts with Kinetochore Protein Iml3 and Promotes Pericentromeric Cohesin

Cited by 17 publications

References 54 publications

Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans

Aft2, a Novel Transcription Regulator, Is Required for Iron Metabolism, Oxidative Stress, Surface Adhesion and Hyphal Development in Candida albicans

Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae

Antimicrobial activity ofMetschnikowia pulcherrimaon wine yeasts

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