Introduction to Fungi, Third Edition

256 ARCHIASCOMYCETES
In the following sections we give brief summaries
of areas in which research on S. pombe is
of outstanding significance for the discipline
of biology as a whole. We anticipate that the
relevance of this yeast for fundamental research
will further increase in the future. Whilst we do
not believe in the concept of a ‘model organism’
or even a ‘model fungus’, it is becoming
clear that S. pombe, based on its more ancestral
position in the phylogenetic system, is in many
ways more relevant to the study of eukaryotic
biology than its great rival, the more derived
Saccharomyces cerevisiae (see p. 270). The entire
genomes of both yeasts have been sequenced,
and research is under way with S. pombe to find
out the minimum number of genes (approximately
17.5% of all genes) required for the
basic functioning of this organism (Decottignies
et al., 2003).
9.3.1 Schizosaccharomyces pombe and
the cell cycle
The term ‘cell cycle’ denotes a carefully controlled
sequence of regulatory and biosynthetic
processes which guide a cell arising from mitosis
towards its division into two daughter cells.
Research on S. pombe has given us a fundamental
understanding of the cell cycle. The literature
on this topic is vast, and it is beyond the scope
of this book to give more than the briefest of
summaries. Our account borrows heavily from
the textbook by Lewin (2000), which also provided
the basis of the diagrammatic summary
(Fig. 9.5).
A young cell arising from mitotic division
starts its life in the G1 phase (G ¼ gap) and may
synthesize RNA, protein and other cellular constituents.
It may grow in size but it does not
duplicate its DNA at this point. The first crucial
control point of the cell cycle is the
START point, located in G1. At this point, the
cell becomes committed to mitosis, and other
options notably sexual reproduction are no
longer available, i.e. beyond the START point the
cell becomes insensitive to mating pheromones.
When DNA duplication is actually initiated,
the cell moves from the G1 to the S (synthesis
of DNA) phase. After DNA replication has been
completed, the G2 phase follows, during
which the S. pombe cell further enlarges in size
and produces all organelles and macromolecules
which are required to support two daughter
cells. A second control point is the boundary
between G2 and the M (mitotic) phase; when
this has been passed, the cell stops elongating.
Condensation and separation of the chromosomes
occur, followed by septation and physical
separation of the two daughter cells. The identification
of genes whose products are involved
in the regulation of the cell cycle was possible
by analysing temperature-sensitive mutants,
i.e. mutants which grow normally at reduced
(permissive) temperature (e.g. 25°C) but are
blocked at some stage of the cell cycle at a
higher (restrictive) temperature (e.g. 37°C).
The most fundamental gene involved in the
cell cycle is cdc2 because its product a protein
kinase is involved at both the START and G2/M
control points, and it is now known to fulfil
the same universal role in all eukaryotes, including
humans (Lee & Nurse, 1987; Nurse, 1990).
In order to act in such a way, the cdc2 protein
(written as Cdc2) combines with different
proteins at specific stages of the cell cycle.
These proteins are termed cyclins because their
levels in the yeast cell show one peak in each cell
cycle, followed by their degradation or inactivity.
There are G1 cyclins and G2 cyclins which have
different properties in combination with Cdc2.
However, the activity of Cdc2 is modulated not
only by the binding of cyclins, but also by kinases
or phosphatases which, respectively, phosphorylate
or dephosphorylate the Cdc2 protein. These
respond to environmental stimuli and often
antagonize each other in their effects on Cdc2.
This allows a fine-tuning of the cell cycle in
response to environmental factors such as the
presence of pheromones which would prevent
progression through START, or nutrient availability.
Whilst the regulation of Cdc2 is relatively
well understood, few of its substrates have
been identified as yet, and this is an area of
ongoing research.
An understanding of the cell cycle of
S. pombe is of significance far beyond mycology
because the principles are conserved across all
eukaryotes. In mammals, one regulatory factor