Molecular characterization of GCD1, a yeast gene required for general control of amino acid biosynthesis and cell-cycle initiation.

The GCD1 gene product of Saccharomyces cerevisiae has been implicated in the coordination of the cell cycle with the general control of amino acid biosynthesis (M. Wolfner et al., J. Mol. Biol. 96:273-290, 1975). Strains containing the gcd1-1 allele constitutively express the amino acid biosynthetic genes at the induced levels normally found only during conditions of amino acid starvation. In addition, gcd1-1 strains do not grow at high temperatures because under these conditions they are unable to proceed beyond the START step of the cell division cycle. We have cloned and sequenced the GCD1 gene and examined various aspects of cellular metabolism in order to elucidate its role(s) in regulating gene expression and the cell cycle. GCD1 encodes a 1.7 kb RNA whose expression is not regulated as a function of amino acid starvation. Overexpression of this RNA does not affect the regulation of amino acid biosynthetic genes or cell growth. GCD1 is an essential gene because cells containing a gcd1-HIS3 disruption are unable to grow. The essential function of GCD1 may be involved in protein synthesis because a gcd1-1 strain incorporates low levels of 35S-methionine into protein when cells are shifted to the restrictive temperature. GCD1 encodes a protein of 511 amino acids whose predicted sequence does not exhibit significant homology to any other known proteins and appears too large to be a ribosomal protein. We suggest that GCD1 encodes a component of the normal protein synthesis machinery that is involved in the translational regulation of GCN4, a protein that coordinately activates the transcription of amino acid biosynthetic genes. GCD1 may also be part of a sensing mechanism in which cells monitor the protein synthesis capacity prior to initiating a new cell division cycle.