A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii

We addressed the role of the centriole-associated EF-hand protein centrin in genomic stability using a Chlamydomonas reinhardtii centrin mutant that forms acentriolar bipolar spindles and lacks the centrin-based rhizoplast structures that join centrioles to the nucleus. Using a genetic assay for loss of heterozygosity, we found that this centrin mutant showed increased genomic instability compared to wild-type cells, and we determined that the increase in genomic instability was due to a 100-fold increase in chromosome loss rates compared to wild type. Live cell imaging reveals an increased rate in cell death during G1 in haploid cells that is consistent with an elevated rate of chromosome loss, and analysis of cell death versus centriole copy number argues against a role for multipolar spindles in this process.The increased chromosome loss rates observed in a centrin mutant that forms acentriolar spindles suggests a role for centrin protein, and possibly centrioles, in mitotic fidelity.Centrioles are cylindrical structures located within the core of the centrosome. Although the localization of centrioles within the centrosome together with their precise duplication prior to mitosis has suggested a role in bipolar spindle assembly or function, the actual role of centrioles in cell division remains unclear and controversial. Cells from which centrioles and centrosomes are ablated can still form bipolar spindles via a centrosome-independent self-organization process, but the effectiveness of such spindles in terms of chromosome segregation has not been carefully measured. Based on the circumstantial evidence that tumor cells which display genomic instability also frequently show aberrations in centriole structure or copy number [1,2], it has been proposed that centrioles may participate in the maintenance of genomic stability. If centrioles play a role in chromosome segregation, then mutations in genes encoding centriolar proteins would be expected to result in genomi