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Cell‐cycle arrest and inhibition of G 1 cyclin translation by iron in AFT1‐1 up yeast
Author(s) -
Philpott Caroline C.,
Rashford Jared,
YamaguchiIwai Yuko,
Rouault Tracey A.,
Dancis Andrew,
Klausner Richard D.
Publication year - 1998
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/17.17.5026
Subject(s) - biology , yeast , translation (biology) , cell cycle , microbiology and biotechnology , saccharomyces cerevisiae , cell cycle checkpoint , cyclin , cell cycle protein , biochemistry , cell , gene , messenger rna
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 G 1 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 G 1 cyclin, cln3‐2 , and expression of the G 1 ‐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.