Biology Reference
In-Depth Information
known to be involved in centrosome regulation and centriole assembly
(Dzhindzhev et al.
2010
). Cep152 associates with Plk4 and is phosphorylated by
this kinase in vitro suggesting that Cep52 can be a substrate of Plk4 (Hatch et al.
2010
). Other kinases and phosphatases, such as CDK11 (Franck et al.
2011
) and
PP2A (Brownlee et al.
2011
) are also involved. Precise dosage of Plk4 is required
to control centriole duplication (Holland et al.
2010
). Accordingly Plk4 over
expression or stabilization induces centrosome amplification (Brownlee et al.
2011
). This is an important link to cancer since the amplification of centrosomes is
a condition found in numerous cancers (reviewed by Chan
2011
). Experiments
based on Xenopus laevis cell-free extracts depletion and reconstitution deliver
unique and highly advantageous possibilities over culture cell transfection to study
this aspect of cell regulation critical for carcinogenesis.
Studies of centrosome duplication revealed few features common with DNA
replication: (i) centrosome duplication and DNA replication must occur once and
only once per cell cycle, (ii) DNA is composed of two strands of nucleotides, the
centrosome is composed of two centrioles, (iii) while DNA replication involves
copying of each strand to create two new double strands, centrosome duplication
implies copying of each centriole to create two new centrosomes. In addition,
Xenopus eggs cell-free extracts studies have shown that the centrosome duplica-
tion is restricted to only one per cell cycle, and similarly to DNA replication is
under a ''licensing control''. Notably, the centrosome duplication licensing is
relieved upon the exit from mitosis by the activity of separase, also involved in
degradation of cohesion required for chromatid separation. The action of separase
on the centrosome results in the disengagement of centrioles allowing a new round
of duplication (Tsou and Stearn 2006) increasing the similarity between the mode
of centrosome and DNA duplication.
Regarding centrosome duplication per se, studies of Plk4 in Xenopus oocytes
revealed that overexpression of the kinase induces de novo centriole formation in a
CDK2-independent manner (Eckerdt et al.
2011
). Thus, de novo formation of
centrioles seems to be under the control of different pathways (CDK2-indepen-
dent) than centriole duplication (CDK2-dependent). A solution for this intriguing
paradox is actively searched nowadays.
20.6 Conclusions
The centrosome research in Xenopus laevis eggs has delivered a number of fun-
damental information on mechanisms governing not only oogenesis, fertilization,
and embryo development, but also different aspects of physiology and pathology
of human cells. This was possible using advantages of functional cell-free extracts
and the injection of living oocytes and embryos with specific blocking antibodies
or morpholino. The field of centrosome research will certainly be followed up in
more detail using human cells. However, we believe the Xenopus laevis egg
studies have not pronounced the last word yet.
