Yeast Genetics and Molecular Biology 1998
College Park, Maryland
August 1998

Name: Philpott, Caroline
Mailing Address: Bldg.10 Rm 9B16 Liver Diseases, NIDDK, NIH, 10 Center Drive, Bethesda, MD 20892-1800, USA
Email Address: philpott@box-p.nih.gov
Phone and Fax numbers: (301)496-1721, (301)402-0491

073

Cell Cycle Arrest and Inhibition of G1 Cyclin Translation by Iron in AFT1-1 up Yeast.


Caroline Philpott (1) , Yuko Yamaguchi-Iwai (1), Tracey Rouault (2), Andrew Dancis (3), Richard Klausner (4)
(1) Bldg.10 Rm 9B16 Liver Diseases, NIDDK, NIH, 10 Center Drive, Bethesda, MD 20892-1800, USA; (2) Bldg. 18-T, Rm 101, NICHD, NIH; (3) 1009 Stellar-Chance Laboratories, 422 Curie Blvd., Philadelphia, PA 19104-6100; (4) Bldg. 18-T, Rm. 101, NICHD, NIH

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 Saccharomyces cerevisiae , 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 , which causes shortening of the G1 phase. This G1 arrest is due to an iron-dependent reduction in the expression of the G1-specific cyclins Cln1 and Cln2. This reduction is not due to changes in transcription of CLN1 or CLN2 , nor is it due to accelerated degradation of Cln2p. Rather, this reduction occurs at the level of Cln2 translation, a previously unreported locus of cell cycle control in yeast.

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