Biology Reference
In-Depth Information
Fig. 12.1 High-risk HPV oncoproteins and centriole alterations. a Normal centriole duplication
is characterized by the assembly of only one new centriole (daughter) with the pre-existing
centriole (mother). b High-risk HPV-16 E7 expression induces centriole multiplication due to
disruption of the centriole duplication cycle and is characterized by the presence of multiple
daughter centrioles at a single maternal centriole. c Expression of high-risk HPV-16 E6 promotes
centriole accumulation due to induction of cytokinesis defects or other cell division errors and
results in cells containing two or more maternal centrioles. d Fluorescence microscopic analysis
of normal duplicated centrioles and 'centriole flower' (centriole multiplication) phenotype
induced by PLK4 overexpression in U-2 OS/centrin-GFP cells
Subsequently, structural proteins are recruited to the nascent pro-centriole to
stabilize and elongate the newly formed daughter centriole. Centrosome duplica-
tion completes during the late G
2
-phase of the cell cycle, when the two fully
formed centriole pairs separate to form the mitotic spindle poles (Azimzadeh and
Bornens
2007
). A more detailed description of centrosome duplication can be
found elsewhere in this topic.
In principal, there are two mechanisms by which centriole amplification may
occur in tumor cells: centriole overduplication and centriole accumulation. These
two phenotypes can be distinguished by the number of older, mature centrioles
present in a cell (Guarguaglini et al.
2005
). Genuine centriole overduplication is
characterized by one or two mature maternal centrioles in the presence of multiple
immature daughter centrioles. In contrast, centriole accumulation is defined by
multiple maternal centrioles with a normal complement of daughter centrioles
(Guarguaglini et al.
2005
). It is important to recognize the distinction between
centriole overduplication and accumulation because cells exhibiting centriole
accumulation may arise due to abortive mitoses or cytokinesis errors and may not
be able to produce viable progeny (Fig.
12.1
). Conversely, cells which exhibit a
genuine centriole overduplication defect are, in general, less genomically altered
and hence are more likely to give rise to genomically unstable daughter cells.
