Differential regulation of two closely clustered yeast genes, MAG1 and DDI1, by cell-cycle checkpoints.
Eukaryotic DNA-damage checkpoint genes have been shown to not only arrest cells at certain stages, but are also involved in the transcriptional response to DNA damage. However, while the signal transduction for cell-cycle checkpoint is well characterized, it is not clear whether the same signal transduction pathway is responsible for the regulation of all DNA damage-inducible genes. In order to understand how different checkpoint genes are involved in gene regulation, the effects of various checkpoint mutations on the expression of a unique yeast MAG1 - DDI1 dual promoter were examined in this study. MAG1 and DDI1 are transcribed from a common promoter region and co-induced by a variety of DNA damaging agents. However, gene-specific cis -acting elements were also identified, and the two genes are indeed differentially expressed under certain conditions. We found that DDI1 induction was not affected in any of the checkpoint mutants. In contrast, MAG1 induction was completely abolished in the pol2 and rad53 mutants. However, in the mec1-1 or any of the G1/S and G2/M checkpoint mutants, including rad9, rad17 and rad24, DNA damage-induced MAG1 expression was not significantly affected, and a rad9 rad17 double mutation only slightly reduced MAG1 induction. Based on this and previous studies, we present two models for the role of checkpoint genes in transcriptional regulation in response to DNA damage.
Zhu
Y
Y
Department of Microbiology and Immunology, University of Saskatchewan, 107 Wiggins Road, Saskatoon,SK S7N 5E5, Canada.
Xiao
W
W
D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D004249:DNA Damage; D045647:DNA Glycosylases; D004260:DNA Repair; D005656:Fungal Proteins / Q000235:genetics*; D016193:G1 Phase / Q000235:genetics; D016195:G2 Phase / Q000235:genetics; D015966:Gene Expression Regulation, Fungal; D005800:Genes, Fungal; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis / Q000235:genetics; D005810:Multigene Family; D016296:Mutagenesis; D009699:N-Glycosyl Hydrolases / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D016196:S Phase / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins
D018797:Cell Cycle Proteins; C108125:DDI1 protein, S cerevisiae; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; C021565:3-methyladenine-DNA glycosylase; D045647:DNA Glycosylases; D009699:N-Glycosyl Hydrolases