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.