ECA39, a conserved gene regulated by c-Myc in mice, is involved in G1/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 level of expression of other genes has opened the field to search for genetic targets for Myc regulation. Recently, using a subtraction/coexpression strategy, a murine genetic target for Myc regulation, called EC439, was isolated. To further characterize the ECA39 gene, we set out to determine the evolutionary conservation of its regulatory and coding sequences. We describe the human, nematode, and budding yeast homologs of the mouse ECA39 gene. Identities between the mouse ECA39 protein and the human, nematode, or yeast proteins are 79%, 52%, and 49%, respectively. Interestingly, the recognition site for Myc binding, located 3' to the start site of transcription in the mouse gene, is also conserved 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 the yeast genome. Disruption of ECA39 which is a recessive mutation that leads to a marked alteration in the cell cycle. Mutant haploids and homozygous diploids have a faster growth rate than isogenic wild-type strains. Fluorescence-activated cell sorter analyses indicate that the mutation shortens the G1 stage in the cell cycle. Moreover, mutant strains show higher rates of UV-induced mutations. The results suggest that the product of ECA39 is involved in the regulation of G1 to S transition.
Schuldiner
O
O
Department of Genetics, Institute of Life Sciences, The Hebrew University of Jerusalem, Givat-Ram, Israel.
Eden
A
A
Ben-Yosef
T
T
Yanuka
O
O
Simchen
G
G
Benvenisty
N
N
D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins; D002453:Cell Cycle / Q000235:genetics*; D017124:Conserved Sequence; D017931:DNA Primers; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics*; D016193:G1 Phase; D005786:Gene Expression Regulation; D005800:Genes, Fungal; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins; D008969:Molecular Sequence Data; D016296:Mutagenesis; D014176:Protein Biosynthesis; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D000637:Transaminases / Q000235:genetics*; D014466:Ultraviolet Rays
D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D005656:Fungal Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D016271:Proto-Oncogene Proteins c-myc; D029701:Saccharomyces cerevisiae Proteins; C490590:BCAT1 protein, human; C094227:Bcat1 protein, mouse; C490588:bcat-1 protein, C elegans; D000637:Transaminases; C101168:BAT1 protein, S cerevisiae