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similar to SAK/PLK4 in C. elegans (O'Connell et al.
2001
) and is required for the
localisation of SAS-4, SAS-5 and SAS-6 (Pelletier et al.
2006
). Asterless/CEP152
has recently been described as a Plk4-interactor that is required for centriole dupli-
cation, being required for SAS-6 localisation to centrioles (Dzhindzhev et al.
2010
;
Guernsey et al.
2010
; Hatch et al.
2010
; Varmark et al.
2007
).
Overexpression of SAK/PLK4, SAS-4 or SAS-6 causes centriole overdupli-
cation (Bettencourt-Dias et al.
2005
; Habedanck et al.
2005
; Kleylein-Sohn et al.
2007
; Peel et al.
2007
; Strnad et al.
2007
), although the structure of centrioles
formed through SAS-4 and SAS-6 overexpression may be abnormal (Kohlmaier
et al.
2009
; Rodrigues-Martins et al.
2007a
). Notably, the centriole overduplication
induced by overexpression of these key regulators involves the formation of
multiple daughters around a single mother in a distinctive 'rosette' arrangement,
rather than the general initiation of de novo centrosome assembly (Kleylein-Sohn
et al.
2007
; Strnad et al.
2007
). However, in cells where there are no centrosomes,
such as unfertilised Drosophila eggs, such overexpression does lead to de novo
centriole assembly (Peel et al.
2007
). These data indicate a limitation of centriole
number that is imposed by a pre-existing mother.
Another element involved in the control of centriole number is the PCM.
Establishment of a PCM cloud is a relatively early event in the de novo centriole
duplication process, after which centrioles arise within the cloud (Khodjakov et al.
2002
). Induction of an expanded PCM in cells with centrioles by overexpression of
pericentrin led to the appearance of multiple daughter centrioles independently of
any spatial or numerical control from the mother centrioles (Loncarek et al.
2008
).
This observation prompted the hypothesis that the mother centriole's principal role
in centriole assembly is the regulation and specification of a PCM scaffold, rather
than the provision of a template (Loncarek et al.
2008
). In either case, the control
of centriole duplication resides in the extant structure.
13.5 Centrosome Amplification
Changes in the coordination of the chromosome and centrosome cycles lead to
centrosome amplification, which has been noted when key cell cycle regulators or
regulatory components of the centrosome are aberrantly expressed or suppressed
(Hergovich et al.
2007
; Hochegger et al.
2007
; Leidel et al.
2005
; McDermott et al.
2006
; Mussman et al.
2000
; Swanton et al.
2007
; Tachibana et al.
2005
). The
altered expression of cell cycle regulators is a frequently observed phenomenon in
human cancers, so this may represent one source of centrosome abnormalities.
Alternatively, the dysregulation of such regulatory genes may occur as a conse-
quence of ongoing genome instability during tumour development.
A further activity that disconnects the chromosome and centrosome cycles
appears to be a controlled response to genotoxic stress. Abnormal amplification of
centrosomes has also been observed following DNA damage induced by irradia-
tion (Dodson et al.
2007
; Sato et al.
2000a
,
b
) or DNA replication stress (Balczon
