Biology Reference
In-Depth Information
Chapter 11
Regulation of Centrosomes
by Cyclin-Dependent Kinases
Rose Boutros
Abstract In eukaryotic cells, each cell division cycle involves two distinct rep-
lication cycles. These are the chromosomal DNA replication and the centrosome
replication cycles. Progression through the cell division cycle is regulated by the
activities of the cyclin-cyclin-dependent kinase complexes. These enzymes con-
trol both DNA replication and centrosome replication and ensure that the two
cycles occur in synchrony.
11.1 CDK-Cyclins and Cell Cycle Progression
Cyclin-dependent kinases (CDKs) are a large family of serine/threonine protein
kinases. The founding member, Cdc2 was identified in genetic screens from yeast
as a mutant that caused cell division cycle defects (Russell and Nurse
1986
). The
human homologue (CDK1) was subsequently identified by its ability to rescue the
yeast Cdc2 mutants (Lee and Nurse
1987
). There are now 11 known genes that
encode CDKs and nine genes that encode CDK-like proteins in mammalian cells
(Malumbres and Barbacid
2005
). The protein products of the best characterised
CDKs control progression through the cell division cycle, in complex with their
regulatory subunits, the cyclins (Fig.
11.1
). Binding of a cyclin to a CDK induces a
conformational change within the active site of the CDK and allows the kinase to
become activated (Bourne et al.
1996
; De Bondt et al.
1993
). Thus, cell cycle
R. Boutros (
)
Children's Medical Research Institute, The University of Sydney,
214 Hawkesbury Road, Westmead, NSW 2145, Australia
e-mail: rboutros@cmri.org.au
&
