A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlam
- PDF / 892,038 Bytes
- 7 Pages / 610 x 792 pts Page_size
- 7 Downloads / 135 Views
BioMed Central
Open Access
Research article
A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii Ivan Zamora and Wallace F Marshall* Address: Dept. of Biochemistry & Biophysics, University of California, San Francisco, 600 16th St., San Francisco, California, 9414, USA Email: Ivan Zamora - [email protected]; Wallace F Marshall* - [email protected] * Corresponding author
Published: 31 May 2005 BMC Biology 2005, 3:15
doi:10.1186/1741-7007-3-15
Received: 15 April 2005 Accepted: 31 May 2005
This article is available from: http://www.biomedcentral.com/1741-7007/3/15 © 2005 Zamora and Marshall; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract Background: The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability. Results: 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. Conclusion: 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.
Background 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 evi-
dence that tumor cells which display genomic instability also frequently show aberrations in centriole structure or copy number [1,2], it has been proposed that cen
Data Loading...
