Biology Reference
In-Depth Information
Papadopoulou
, 2008). Cdc5p has similar regulatory roles in budding yeast,
binding to, and phosphorylating Ndd1p to stimulate its own and other genes' cell
cycle expression (Darieva
et al.
, 2006). Related mechanisms also occur in
humans with polo kinases phosphorylating FoxM1 forkhead-like transcription
factors (Fu
et al.
et al.
, 2008) which control cyclin and polo kinase gene expression
(Alvarez
, 2005). Thus, polo kinases, known to have
primary roles in controlling events through mitosis and cytokinesis, cause this to
occur in part through regulating expression of genes required at this cell cycle
time.
et al.
, 2001; Laoukili
et al.
A different example of phase-specific expression being important for
cell cycle control is shown by the fission yeast gene
mik1
þ
encodes a
protein kinase that phosphorylates the fission yeast CDK, Cdc2p, to inhibit its
activity and so prevent mitotic entry, thus functioning at the G2-M boundary
(Lee
mik1
þ
.
mik1
þ
mRNA and protein levels peak at the G1-S boundary, and that it is under MBF/
MCB controls (Baber-Furnari
et al.
, 1994). It was a surprise, therefore, when it was found that
,
2001). The explanation for this is that Mik1p protein is produced during S phase
as part of the mechanism to prevent M phase from occurring before DNA
synthesis is complete. Thus, the specific production of Mik1p protein during S
phase by transcriptional regulation is part of the control mechanism that ensures
orderly entry into the following M phase, later in the cell cycle.
et al.
, 2000; Christensen
et al.
, 2000; Ng
et al.
VI. UNIMPORTANCE OF CELL CYCLE REGULATED GENE EXPRESSION
Despite the fact that some genes are periodically expressed in both yeast species,
and in a few cases this is significant for cell cycle controls, it is important to
realize that in many other cases, indeed the majority, periodic expression of genes
appears to be irrelevant to cell cycle progression, at least under experimental
conditions. This conclusion can be stated because of observation from two types
of experimental approaches.
The first approach is to ask the simple question whether an individual
gene's periodic expression is significant, by replacing its promoter with another
constitutively active one, resulting in the gene being expressed throughout the
cell cycle. It is surprising on how many occasions this experiment has little or no
effect on cell division. Perhaps even more striking, however, is when cell cycle
transcription factors are either deleted from the chromosome or modified to
become constitutively activated, resulting in gross effects on the expression of
their whole target group. In many cases when this is done, not only are the cells
still alive but often they also complete reasonably normal cell cycles. Examples of
this include from budding yeast, deleting the genes encoding Swi4p, Swi6p,
Fkh1p, and Fkh2p (Pic
et al.
, 2000); and from fission yeast, Res1p, Res2p,
