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Berthelet S, et al.  (2010) Functional Genomics Analysis of the Saccharomyces cerevisiae Iron Responsive Transcription Factor Aft1 Reveals Iron-Independent Functions. Genetics 185(3):1111-28

Abstract: The Saccharomyces cerevisiae transcription factor Aft1 is activated in iron-deficient cells to induce the expression of iron regulon genes, which coordinate the increase of iron uptake and remodel cellular metabolism to survive low iron conditions. In addition, Aft1 has been implicated in numerous cellular processes including cell cycle progression and chromosome stability; however, it is unclear if all cellular effects of Aft1 are mediated through iron homeostasis. To further investigate the cellular processes impacted by Aft1, we identified greater than 70 deletion mutants that are sensitive to perturbations in AFT1 levels using genome-wide synthetic lethal and synthetic dosage lethal screens. Our genetic network reveals that Aft1 impacts a diverse range of cellular processes, including the RIM101 pH pathway, cell wall stability, DNA damage, protein transport, chromosome stability and mitochondrial function. Surprisingly, only a subset of mutants identified are sensitive to extracellular iron fluctuations or display genetic interactions with mutants of iron regulon genes AFT2 or FET3. We demonstrate that Aft1 works in parallel with the RIM101 pH pathway and the role of Aft1 in DNA damage repair is mediated by iron. In contrast, through both directed studies and microarray transcriptional profiling, we show that the role of Aft1 in chromosome maintenance and benomyl resistance is independent of its iron regulatory role, potentially through a non-transcriptional mechanism.

Status: Published Type: Journal Article PubMed ID: 20439772

Topics addressed in this paper

Number of different genes curated to this paper: 105

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Topics Topics not linked to Genes Genes linked to topics (#1 - 10 )
AFT1 AFT2 BSC4 CBF1 CCS1 CCW12 CDC50 CDH1 CEM1 CHO2
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Function/Process blue ball
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Topics Genes linked to topics (#11 - 20 )
CKB1 CKB2 CLN2 CTF13 CTF19 CYT2 DEP1 DRS2 FET3 FET4
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Topics Genes linked to topics (#21 - 30 )
FTR1 GAS1 GDS1 GEP4 GEP7 GRX8 HOM3 HTD2 HTZ1 HUR1
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Topics Genes linked to topics (#31 - 40 )
IMG2 IML3 IRA2 LGE1 LPD1 LST8 MCM16 MCM21 MCM22 MCT1
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Topics Genes linked to topics (#41 - 50 )
MDM10 MED1 MET14 MET3 MET5 MGR1 MIT1 MMS22 MNS1 MRE11
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Topics Genes linked to topics (#51 - 60 )
MRH4 MRP49 MRS2 MSR1 MTC3 MZM1 NEM1 OMS1 PEP12 PMR1
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Topics Genes linked to topics (#61 - 70 )
PTH1 RAD27 RCF1 RCF2 REX4 RIB4 RIM1 RIM101 RIM11 RIM20
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Topics Genes linked to topics (#71 - 80 )
RIM21 RIM9 RPN4 RPS21B RXT2 SAC7 SHU2 SNF5 SPE2 SPO77
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Topics Genes linked to topics (#81 - 90 )
SRN2 SSH1 STP22 SWC3 SWR1 SYN8 TEF4 TIM18 TPS1 TPS2
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Topics Genes linked to topics (#91 - 100 )
VPS24 VPS3 VPS36 VPS52 VPS60 VPS72 VRP1 YDR269C YHL005C YJR120W
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Topics Genes linked to topics (#101 - 105 )
YML090W YNL235C YOL050C YOR331C YPS3
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