CDC function in vertebrates
Six protein kinases that belong to the family of cdc2-related kinases have
been identified in Caenorhabditis elegans. Results from RNA interference
experiments indicate that at least one of these kinases is required for
cell-cycle progression during meiosis and mitosis. This kinase, encoded by
the ncc-1 gene, is closely related to human Cdk1/Cdc2, Cdk2 and Cdk3 and
yeast CDC28/cdc2+. It was asked whether ncc-1 acts to promote passage
through a single transition or multiple transitions in the cell cycle,
analogous to Cdks in vertebrates or yeasts. Five recessive ncc-1 mutations
were isolated in a genetic screen for mutants that resemble larval arrested
ncc-1(RNAi) animals. The results indicate that maternal ncc-1 product is
sufficient for embryogenesis, and that zygotic expression is required for
cell divisions during larval development. Cells that form the postembryonic
lineages in wild-type animals do not enter mitosis in ncc-1 mutants, as
indicated by lack of chromosome condensation and nuclear envelope breakdown.
However, progression through G1 and S phase appears unaffected, as revealed
by expression of ribonucleotide reductase, incorporation of BrdU and DNA
quantitation. These results indicate that C. elegans uses multiple Cdks to
regulate cell-cycle transitions and that ncc-1 is the C. elegans ortholog of
Cdk1/Cdc2 in other metazoans, required for M phase in meiotic as well as
mitotic cell cycles (Boxem, 1999).

Following ncc-1 RNAi treatment, fertilized oocytes fail to complete meiotic
maturation. At the time of injection, a large number of germ precursor cells
are in pachytene of meiosis I. These nuclei progress through meiotic
prophase I but do not initiate metaphase, indicating that ncc-1 is required
to promote the transition from prophase to metaphase in meiosis. A role in
meiosis is consistent with the function of Cdk1/Cdc2 in other eukaryotes. In
fact, Xenopus p34cdc2 was discovered by the biochemical characterization of
maturation promoting factor (MPF), a cytoplasmic factor that induces meiotic
maturation when injected into immature oocytes. Completion of meiosis I and
II is a two step process in amphibians. Progesterone, or injection of MPF,
triggers oocytes that are arrested in diplotene of prophase I to progress
through meiosis I. Mature oocytes will subsequently arrest in metaphase of
meiosis II and can be triggered by fertilization to complete meiosis.
Meiotic maturation in C. elegans is induced by a factor in sperm that is
independent from the sperm’s function at fertilization. In the absence of
sperm, C. elegans oocytes arrest for prolonged periods in diakinesis. Future
studies may reveal whether progesterone and the ‘sperm factor’ activate
similar pathways that induce p34cdc2 and ncc-1, respectively, and trigger
progression to meiotic metaphase I (Boxem, 1999 and references).

Does progression through meiotic prophase require ncc-1 function? In the
RNA-injected animals, oocyte development appears normal and chromosomes
become fully condensed. It cannot be exclude that inactivation of ncc-1 by
RNAi is incomplete. However, several observations support effective
inactivation. If inactivation was complete, entry into meiotic development,
meiotic prophase progression, condensation of chromosomes to diakinesis
bivalents and oocyte development can all occur independent of ncc-1. If
these processes do require ncc-1 activity, this must be less activity than
required for germ cell proliferation and for the transition from diakinesis
to meiosis I. As yet, formation of diakinesis bivalents of normal morphology
in the absence of Cdk1 activity has not been described in any eukaryote.
During spermatogenesis in Drosophila, DNA condensation can occur in the
apparent absence of Dmcdc2 activity. However, male meiosis in Drosophila
does not involve meiotic recombination and attachment of bivalents by
chiasmata. Nuclear envelope breakdown occurs slowly in mature ncc-1( RNAi)
oocytes; by the time it is accomplished, meiosis would normally have been
completed. The fact that degradation still occurs could indicate incomplete
inactivation of ncc-1, as Cdk1 is believed to phosphorylate nuclear lamins
and to trigger nuclear envelope breakdown in mitosis. However, other kinases
have also been implicated in nuclear lamin phosphorylation, including S6
kinase II and protein kinase C. Such kinases may trigger nuclear envelope
breakdown in the absence of ncc-1 activity (Boxem, 1999).