Cell-cycle arrest and inhibition of G1 cyclin translation by iron in AFT1-1(up) yeast.
Although iron is an essential nutrient, it is also a potent cellular toxin, and the acquisition of iron is a highly regulated process in eukaryotes. In yeast, iron uptake is homeostatically regulated by the transcription factor encoded by AFT1. Expression of AFT1-1(up), a dominant mutant allele, results in inappropriately high rates of iron uptake, and AFT1-1(up) mutants grow slowly in the presence of high concentrations of iron. We present evidence that when Aft1-1(up) mutants are exposed to iron, they arrest the cell division cycle at the G1 regulatory point Start. This arrest is dependent on high-affinity iron uptake and does not require the activation of the DNA damage checkpoint governed by RAD9. The iron-induced arrest is bypassed by overexpression of a mutant G1 cyclin, cln3-2, and expression of the G1-specific cyclins Cln1 and Cln2 is reduced when yeast are exposed to increasing amounts of iron, which may account for the arrest. This reduction is not due to changes in transcription of CLN1 or CLN2, nor is it due to accelerated degradation of the protein. Instead, this reduction occurs at the level of Cln2 translation, a recently recognized locus of cell-cycle control in yeast.
Philpott
C C
CC
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-5430, USA. carolinep@intra.niddk.nih.gov
Rashford
J
J
Yamaguchi-Iwai
Y
Y
Rouault
T A
TA
Dancis
A
A
Klausner
R D
RD
D001692:Biological Transport; D016213:Cyclins / Q000096:biosynthesis*; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics*; D016193:G1 Phase / Q000187:drug effects; D015966:Gene Expression Regulation, Fungal; D006706:Homeostasis; D007501:Iron / Q000633:toxicity*; D008957:Models, Genetic; D009154:Mutation; D014176:Protein Biosynthesis; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000187:drug effects; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors / Q000235:genetics*; D000091346:Tripeptidyl-Peptidase 1
C090297:AFT1 protein, S cerevisiae; C082719:CLN1 protein, S cerevisiae; C082721:CLN2 protein, S cerevisiae; C079895:CLN3 protein, S cerevisiae; D016213:Cyclins; D005656:Fungal Proteins; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D000091346:Tripeptidyl-Peptidase 1; D007501:Iron