Biology Reference
In-Depth Information
ABSTRACT
The regulation of gene expression through the mitotic cell cycle, so that genes
are transcribed at particular cell cycle times, is widespread among eukaryotes. In
some cases, it appears to be important for control mechanisms, as deregulated
expression results in uncontrolled cell divisions, which can cause cell death,
disease, and malignancy. In this review, I describe the current understanding of
such regulated gene expression in two established simple eukaryotic model
organisms, the budding yeast
Saccharomyces cerevisiae
and the fission yeast
Schi-
zosaccharomyces pombe
. In these two yeasts, the global pattern of cell cycle gene
expression has been well described, and most of the transcription factors that
control the various waves of gene expression, and how they are in turn them-
selves regulated, have been characterized. As related mechanisms occur in all
other eukaryotes, including humans, yeasts offer an excellent paradigm to under-
stand this important molecular process.
2011, Elsevier Inc.
I. INTRODUCTION
A. Cell cycle controls
How a cell duplicates and divides is a major area of interest in biology, not only
because the process is so incredibly accurate and complex, and so of inherent
fascination in its own right, but also because defects in the process are the basis
for many human diseases.
Traditionally, the eukaryotic mitotic cell cycle is divided into four
separate, consecutive, and distinct stages: S phase (where DNA replication
occurs) and M phase (where the chromosomes separate), with these two sepa-
rated by gap phases called G1 and G2. Research in many organisms, from simple
yeasts to much more complex eukaryotes, including humans, has revealed that
the cell division cycle is controlled in many ways and at many levels. As a
generalization, this complexity of control seems to be to ensure that cell division
occurs in a highly reproducible and accurate way, with multiple levels of controls
introducing “double check” and “fail-safe” processes. The various types of control
mechanisms include changes in protein activity through posttranslational modi-
fication (such as phosphorylation), changes in protein stability (in some cases
through specific, targeted degradation), and changes in protein distribution. It is
important to emphasize that although the regulation of gene expression through
transcription offers yet another important layer of control, it is just part of an
overall complex array of multiple control mechanisms.
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