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Fig. 13.1 Current models for centrosome amplification pathways: multiple centrosomes may be
generated a during a prolonged cell cycle arrest, by templated centrosome duplication; b upon
loss of existing centrioles, by a de novo pathway; c following DNA-damaging treatment by
centrosome fragmentation; and d through the formation of multiple daughters from a single
mother. Parental centrioles are schematically represented by rectangles coloured light blue for the
mother, and dark blue for daughter centrioles. Red spots indicate centrobin association with
centrioles during the cell cycle (Zou et al. 2005 ) and green spots indicate Cep170 localisation at
the mature centriole (Guarguaglini et al. 2005 ; Saladino et al. 2009 )
that an arrest in G2 phase after IR is permissive for the overduplication of the
centrosome, as we have proposed (Dodson et al. 2004 ).
Although an extended G2 phase delay is necessary for DNA damage-induced
centrosome overduplication, a question that remains is whether such an arrest is
sufficient. Chk1 localises to the centrosome, along with many other elements of the
DNA damage response (Loffler et al. 2006 ; Oricchio et al. 2006 ), so that it has been
technically challenging to address this issue. Inhibition of CDK1 by pharmaco-
logical means or by the use of an analogue-sensitive mutant causes a robust cell
cycle arrest at the transition to mitosis, without any DNA damage signal, which is
accompanied by high levels of centrosome amplification (Hochegger et al. 2007 ).
However, CDK1 inhibition also elevates the activity of CDK2 (Bourke et al. 2010 ).
Notably, IR also causes the activation of CDK2 activity in a subset of cell types
(Bourke et al. 2010 ), so that of the conditions for centrosome amplification that we
have outlined, DNA damage leads to the fulfilment of several at once.
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