Biology Reference
In-Depth Information
Chapter 13
Centrosomes, DNA Damage
and Aneuploidy
Chiara Saladino, Emer Bourke and Ciaran G. Morrison
Abstract Understanding how the genomic instability that accompanies tumour
development arises has been an important question for more than a century. One
potential cause of such instability is defective chromosome segregation during
mitosis. A cause of mitotic defects may lie in the acquisition of multiple mitotic
spindle poles, through an increase in the number of centrosomes. Cancer cells
frequently possess multiple centrosomes. DNA damaging treatments, or mutations
in key DNA repair genes, also lead to centrosome amplification. Here, we review
current models for how cells may lose the normal controls on centrosome dupli-
cation and acquire more than the normal number of these organelles. We also
discuss how genotoxic stresses may contribute to the dysregulation of centrosome
duplication
and
how
this
process
may
be
a
contributory
factor
in
cellular
transformation.
13.1 Mechanisms of Aneuploidy
Aneuploidy has been described as the most common characteristic of cancer cells
(Weaver and Cleveland
2006
). Numerous genetic alterations have been observed
in neoplastic cells, including chromosome and gene deletions, amplification and
translocation. However, the presence of these alterations does not necessarily
C. Saladino
C. G. Morrison (
&
)
School of Natural Sciences, Centre for Chromosome Biology,
National University of Ireland Galway, Galway, Ireland
e-mail: Ciaran.Morrison@nuigalway.ie
E. Bourke
Institute of Technology Sligo, Ash Lane, Sligo, Ireland
