TY - JOUR
T1 - Aneuploidy and chromosomal instability
T2 - A vicious cycle driving cellular evolution and cancer genome chaos
AU - Potapova, Tamara A.
AU - Zhu, Jin
AU - Li, Rong
N1 - Funding Information:
Acknowledgments We would like to thank Guangbo Chen and members of the Rong Li lab for their insightful discussions, Gary Gorbsky for comments on the manuscript, and Mary Toth for help with review preparation. This work was supported by the NIH grant RO1-GM059964 to Rong Li. Tamara Potapova was supported by a Postdoctoral Fellowship, PF-12-129-01-CCG from the American Cancer Society. Jin Zhu is a graduate student registered with the Open University.
PY - 2013/12
Y1 - 2013/12
N2 - Aneuploidy and chromosomal instability frequently co-exist, and aneuploidy is recognized as a direct outcome of chromosomal instability. However, chromosomal instability is widely viewed as a consequence of mutations in genes involved in DNA replication, chromosome segregation, and cell cycle checkpoints. Telomere attrition and presence of extra centrosomes have also been recognized as causative for errors in genomic transmission. Here, we examine recent studies suggesting that aneuploidy itself can be responsible for the procreation of chromosomal instability. Evidence from both yeast and mammalian experimental models suggests that changes in chromosome copy number can cause changes in dosage of the products of many genes located on aneuploid chromosomes. These effects on gene expression can alter the balanced stoichiometry of various protein complexes, causing perturbations of their functions. Therefore, phenotypic consequences of aneuploidy will include chromosomal instability if the balanced stoichiometry of protein machineries responsible for accurate chromosome segregation is affected enough to perturb the function. The degree of chromosomal instability will depend on specific karyotypic changes, which may be due to dosage imbalances of specific genes or lack of scaling between chromosome segregation load and the capacity of the mitotic system. We propose that the relationship between aneuploidy and chromosomal instability can be envisioned as a "vicious cycle," where aneuploidy potentiates chromosomal instability leading to further karyotype diversity in the affected population.
AB - Aneuploidy and chromosomal instability frequently co-exist, and aneuploidy is recognized as a direct outcome of chromosomal instability. However, chromosomal instability is widely viewed as a consequence of mutations in genes involved in DNA replication, chromosome segregation, and cell cycle checkpoints. Telomere attrition and presence of extra centrosomes have also been recognized as causative for errors in genomic transmission. Here, we examine recent studies suggesting that aneuploidy itself can be responsible for the procreation of chromosomal instability. Evidence from both yeast and mammalian experimental models suggests that changes in chromosome copy number can cause changes in dosage of the products of many genes located on aneuploid chromosomes. These effects on gene expression can alter the balanced stoichiometry of various protein complexes, causing perturbations of their functions. Therefore, phenotypic consequences of aneuploidy will include chromosomal instability if the balanced stoichiometry of protein machineries responsible for accurate chromosome segregation is affected enough to perturb the function. The degree of chromosomal instability will depend on specific karyotypic changes, which may be due to dosage imbalances of specific genes or lack of scaling between chromosome segregation load and the capacity of the mitotic system. We propose that the relationship between aneuploidy and chromosomal instability can be envisioned as a "vicious cycle," where aneuploidy potentiates chromosomal instability leading to further karyotype diversity in the affected population.
KW - Aneuploidy
KW - Chromosomal instability
KW - Gene dosage
KW - Mitotic checkpoint
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U2 - 10.1007/s10555-013-9436-6
DO - 10.1007/s10555-013-9436-6
M3 - Article
C2 - 23709119
AN - SCOPUS:84890312311
SN - 0167-7659
VL - 32
SP - 377
EP - 389
JO - Cancer and Metastasis Reviews
JF - Cancer and Metastasis Reviews
IS - 3-4
ER -