ECA39, A CONSERVED GENE REGULATED BY C-MYC IN MICE, IS INVOLVED IN G(1) S CELL-CYCLE REGULATION IN YEAST/

The c-myc oncogene has been shown to play a role in cell proliferation and apoptosis. The realization that myc oncogenes may control the lev el of expression of other genes has opened the field to search for gen etic targets for Myc regulation. Recently, using a subtraction/coexpre ssion strategy, a murine genetic target for Myc regulation, called ECA 39, was isolated. To further characterize the ECA39 gene, we set out t o determine the evolutionary conservation of its regulatory and coding sequences. We describe the human, nematode, and budding yeast homolog s of the mouse ECA39 gene. Identities between the mouse ECA39 protein and the human, nematode, or yeast proteins are 79%, 52%, and 49%, resp ectively. Interestingly, the recognition site for Myc binding, located 3' to the start site of transcription in the mouse gene, is also cons erved in the human homolog. This regulatory element is missing in the ECA39 homologs from nematode or yeast, which also lack the regulator c -myc. To understand the function of ECA39, we deleted the gene from th e yeast genome, Disruption of ECA39 which is a recessive mutation that leads to a marked alteration in the cell cycle. Mutant haploids and h omozygous diploids have a faster growth rate than isogenic wild-type s trains. Fluorescence-activated cell sorter analyses indicate that the mutation shortens the G(1) stage in the cell cycle. Moreover, mutant s trains show higher rates of UV-induced mutations. The results suggest that the product of ECA39 is involved in the regulation of G(1) to S t ransition.