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Open Access Highly Accessed Research

Rapid telomere motions in live human cells analyzed by highly time-resolved microscopy

Xueying Wang13, Zvi Kam2, Peter M Carlton1, Lifeng Xu1, John W Sedat1 and Elizabeth H Blackburn1*

Author Affiliations

1 Department of Biochemistry and Biophysics, University of California at San Francisco, California, USA

2 Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel

3 Genome Institute of Singapore, Singapore

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Epigenetics & Chromatin 2008, 1:4  doi:10.1186/1756-8935-1-4

Published: 27 October 2008

Abstract

Background

Telomeres cap chromosome ends and protect the genome. We studied individual telomeres in live human cancer cells. In capturing telomere motions using quantitative imaging to acquire complete high-resolution three-dimensional datasets every second for 200 seconds, telomere dynamics were systematically analyzed.

Results

The motility of individual telomeres within the same cancer cell nucleus was widely heterogeneous. One class of internal heterochromatic regions of chromosomes analyzed moved more uniformly and showed less motion and heterogeneity than telomeres. The single telomere analyses in cancer cells revealed that shorter telomeres showed more motion, and the more rapid telomere motions were energy dependent. Experimentally increasing bulk telomere length dampened telomere motion. In contrast, telomere uncapping, but not a DNA damaging agent, methyl methanesulfonate, significantly increased telomere motion.

Conclusion

New methods for seconds-scale, four-dimensional, live cell microscopic imaging and data analysis, allowing systematic tracking of individual telomeres in live cells, have defined a previously undescribed form of telomere behavior in human cells, in which the degree of telomere motion was dependent upon telomere length and functionality.