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Mol. Cell. Biol., 11 1995, 5917-5928, Vol 15, No. 11
H Althoefer, A Schleiffer, K Wassmann, A Nordheim and G Ammerer
In the budding yeast Saccharomyces cerevisiae, MCM1 encodes an essential
DNA-binding protein that regulates transcription of many genes in
cooperation with different associated factors. With the help of a
conditional expression system, we show that Mcm1 depletion has a distinct
effect on cell cycle progression by preventing cells from undergoing
mitosis. Genes that normally exhibit a G2-to-M-phase- specific expression
pattern, such as CLB1, CLB2, CDC5, SWI5, and ACE2, remain uninduced in the
absence of functional Mcm1. In vivo footprinting experiments show that
Mcm1, in conjunction with an Mcm1- recruited factor, binds to the promoter
regions of SWI5 and CLB2 at sites shown to be involved in cell cycle
regulation. However, promoter occupation at these sites is cell cycle
independent, and therefore the regulatory system seems to operate on
constitutively bound Mcm1 complexes. A gene fusion that provides Mcm1 with
a strong transcriptional activation domain causes transcription of SWI5,
CLB1, CLB2, and CDC5 at inappropriate times of the cell cycle. Thus, Mcm1
and a cooperating, cell cycle-regulated activation partner are directly
involved in the coordinated expression of multiple G2-regulated genes. The
arrest phenotype of Mcm1-depleted cells is consistent with low levels of
Clb1 and Clb2 kinase. However, constitutive CLB2 expression does not
suppress the mitotic defect, and therefore other essential activities
required for the G2-to-M transition must also depend on Mcm1 function.
Copyright © 1995, American Society for Microbiology
Mcm1 is required to coordinate G2-specific transcription in Saccharomyces cerevisiae
Institute for Molecular Biology, Hannover Medical School, Germany.
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