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Mol Cell Biol. Jun 1997; 17(6): 3356–3363.
PMCID: PMC232188

Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe.

Abstract

Exposure of mammalian cells to UV irradiation or alkylating agents leads to the activation of the c-Jun N-terminal kinase and p38 stress-activated protein kinase cascades, phosphorylation of c-Jun and ATF-2 bZIP transcription factors, and finally to selective induction of gene expression. This UV response is believed to be crucially important for cell survival, although conclusive evidence is lacking. Here, we address this issue by investigating a homologous UV response pathway in the fission yeast Schizosaccharomyces pombe. In fission yeast cells, UV irradiation induces activation of Spc1 stress-activated protein kinase, which in turn phosphorylates the Atf1 bZIP transcription factor. spc1 mutants are hypersensitive to killing by UV at a level equivalent to some checkpoint rad mutants. Whereas checkpoint rad mutants fail to arrest division in response to DNA damage, spc1 mutants are defective at resuming cell division after UV exposure. Levels of basal and UV-induced transcription of ctt1+, which encodes a catalase believed important for combating oxidative stress caused by UV, are extremely low in spc1 mutants. Atf1 is required for UV-induced transcription of ctt1+, but atf1 mutants are not hypersensitive to killing by UV. This surprising finding is explained by the observation that ctt1+ basal expression is unaffected in atf1 single mutant and spc1 atf1 double mutant cells, suggesting that unphosphorylated Atf1 represses ctt1+ expression in spc1 cells. In fact, the level of UV sensitivity of spc1 atf1 double mutant cells is intermediate between those of the wild type and spc1 mutants. These findings suggest the following. (i) Key properties of UV response mechanisms are remarkably similar in mammals and S. pombe. (ii) Activation of Spc1 kinase greatly enhances survival of UV-irradiated cells. (iii) Induction of gene expression by activation of Atf1 may not be the most important mechanism by which stress-activated kinases function in the UV response.

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Selected References

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