Question

What will happen if the number of centrioles inside a cell increases significantly?

Answer 1

Centrosome duplication is controlled by centriole replication. In most dividing animal cells, centrioles duplicate only once per cell cycle at a site adjacent to existing centrioles. Ifcentrioles number increases Extra copies of centrosomes frequently result in errors in spindle assembly that give rise to chromosome missegregation and the production of aneuploid daughter cellsAlmost one hundred years ago, Theodor Boveri proposed that centrosome amplification can contribute to tumorigenesis Since then supernumerary centrosomes have been reported in a variety of different tumor cells in vitro and in vivo and are a consistent feature of aneuploid tumors. However, despite the large body of circumstantial evidence linking extra centrosomes to the development of cancer, it remains unclear whether supernumerary centrosomes actively contribute to tumorigenesis or arise as a byproduct of cellular transformation.




The functional role of centrioles or basal bodies in mitotic spindle assembly and function is currently unclear. Although supernumerary centrioles have been associated with multipolar spindles in cancer cells, suggesting centriole number might dictate spindle polarity, bipolar spindles are able to assembly in the complete absence of centrioles, suggesting a level of centriole-independence in the spindle assembly pathway. In this report we perturb centriole number using mutations in Chlamydomonas reinhardtii, and measure the response of the mitotic spindle to these perturbations in centriole number.


Although altered centriole number increased the frequency of monopolar and multipolar spindles, the majority of spindles remained bipolar regardless of the centriole number. But even when spindles were bipolar, abnormal centriole numbers led to asymmetries in tubulin distribution, half-spindle length and spindle pole focus. Half spindle length correlated directly with number of centrioles at a pole, such that an imbalance in centriole number between the two poles of a bipolar spindle correlated with increased asymmetry between half spindle lengths. These results are consistent with centrioles playing an active role in regulating mitotic spindle length. Mutants with centriole number alteration also show increased cytokinesis defects, but these do not correlate with centriole number in the dividing cell and may therefore reflect downstream consequences of defects in preceding cell divisions.