INTRODUCTION
Cyclin-dependent kinases (CDKs)
1
are required for the onset
of S phase and M phase of the mitotic cell cycle (reviewed by
Nurse, 2000). In higher eukaryotes, distinct CDKs associate
with several cyclins to control the G
1
/S transition, whereas
cdk1/cyclin B is specifically required to control the G
2
/M
transition (reviewed by Nigg, 1995). In the fission yeast
Schizosaccharomyces pombe, cdc2p/cdc13p complex controls
the G
2
/M transition of the cell cycle, whereas cig2p B-type
cyclin associates with cdc2p to promote the G
1
/S transition,
although this can be accomplished by the cig1p and cdc13p B-
type cyclins (Fisher and Nurse, 1996; Mondesert et al., 1996).
Fission yeast possesses two other cyclins, puc1p and pas1p,
which are related to the Cln1-3p G
1
cyclins of Saccharomyces
cerevisiae (Forsburg and Nurse, 1991; Tanaka and Okayama,
2000). Puc1p may regulate the G
1
phase progression in
response to cell size (Martin-Castellanos et al., 2000), whereas
pas1p associates with a second non-essential CDK, pef1p, to
activate the res2p-cdc10p transcriptional complex at the
START point of the cell cycle (Tanaka and Okayama, 2000).
CDKs are not only required for the onset of S phase and M
phase of the mitotic cell cycle but also are involved in the
regulation of centrosomes and microtubule (MT) dynamics. In
Xenopus egg extracts, CDKs induce a change in MT dynamics
and steady-state length (Verde et al., 1990). Cytostatic factor-
arrested Xenopus egg extracts (which contain active cdc2
kinase bound to cyclin), but not interphase extracts, can convert
fission yeast spindle pole bodies (SPBs, the equivalent of
animal centrosomes) to a nucleation competent state (Masuda
et al., 1992). However, purified cdc2/cyclin B1 complex was
unable to do so, suggesting that other factors besides cdc2
kinase are also required for SPB activation (Masuda et
al., 1992). In multicellular eukaryotes, duplication of the
centrosome requires cdk2/cyclin E activity (reviewed by
Whitehead and Salisbury, 1999; Meraldi et al., 1999; Okuda
et al., 2000). Cdk1 localises to spindle MTs and metazoa
centrosomes via association with MT-associated proteins
(MAPs), whose phosphorylation induces a change in MT
dynamics at the onset of mitosis (reviewed by Andersen, 2000).
In fission yeast, Alfa et al. showed by immunofluorescence that
cdc2p and cdc13p are localised to the SPBs during mitosis
(Alfa et al., 1990). In a more recent paper, cdc13-GFP fusion
was shown to localise on the SPBs and the spindle from
prophase to metaphase (Yanagida et al., 1999).
S. pombe cdc2p is also required during the meiotic cell cycle
for premeiotic DNA synthesis, the second division and, very
likely, the first meiotic division (reviewed by Murakami
and Nurse, 2000). Once karyogamy and premeiotic DNA
replication have occurred, the meiotic prophase nucleus shows
an elongated morphology, called a ‘horse-tail’, and oscillates
back and forth between the cell poles (reviewed by Hiraoka,
1998). During this horse-tail movement, telomeres are
clustered at the SPB in a bouquet-like arrangement at the
2627
We investigated the in vivo localisation of fission yeast
cyclin-dependent kinase cdc2p during mitosis and meiosis.
Fusion to yellow fluorescent protein (YFP) revealed that
cdc2-YFP is present in the cytoplasm at all stages of the cell
cycle. Nuclear cdc2-YFP fluorescence oscillates with that of
cdc13-YFP cyclin. At G
1
/S, at least one of cdc13p, cig1p or
cig2p B-type cyclins is required for the accumulation of
cdc2-YFP into the nucleus. Cdc2-YFP and cdc13-YFP are
highly enriched on the spindle pole body of cells in late G
2
or arrested at S phase. Both accumulate on the spindle pole
bodies and the spindle in prophase and metaphase
independently of the microtubule-associated protein dis1p.
In anaphase, the cdc2p/cdc13p complex leaves the spindle
prior to sister chromatid separation, and cdc13-YFP is
enriched at the nuclear periphery before fluorescence
disappears. If cdc13p cannot be recognized by the
anaphase-promoting complex, cdc2-YFP and cdc13-YFP
remain associated with the spindle. In mating cells, cdc2-
YFP enters the nucleus as soon as the cells undergo fusion.
During karyogamy and meiotic prophase, cdc2-YFP is
highly enriched on the centromeres. In meiosis I,
association of cdc2-YFP with the spindle and the spindle
pole bodies shows differences to mitotic cells, suggesting
different mechanisms of spindle formation. This study
suggests that changes in cdc2p localisation are important
for both mitosis and meiosis regulation.
Key words: Schizosaccharomyces pombe, Mitosis, Meiosis, Cyclins,
Cyclin-dependent kinase
SUMMARY
In vivo localisation of fission yeast cyclin-dependent
kinase cdc2p and cyclin B cdc13p during mitosis and
meiosis
Anabelle Decottignies*, Patrick Zarzov and Paul Nurse
Cell Cycle Laboratory, Imperial Cancer Research Fund, London, WC2A 3PX, UK
*Author for correspondence (e-mail: a.decottignies@icrf.icnet.uk)
Accepted 23 April 2001
Journal of Cell Science 114, 2627-2640 (2001) © The Company of Biologists Ltd
RESEARCH ARTICLE