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Mol. Cell. Biol., 06 1997, 3356-3363, Vol 17, No. 6
G Degols and P Russell
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.
Copyright © 1997, American Society for Microbiology
Discrete roles of the Spc1 kinase and the Atf1 transcription factor in the UV response of Schizosaccharomyces pombe
Department of Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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