QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

Vol. 20, Issue 10, 2563-2571, May 15, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-10-1019v1 20/10/2563    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cooley, C. Articles by Morrison, C. G. Search for Related Content PubMed PubMed Citation Articles by Cooley, C. Articles by Morrison, C. G.

Trf1 Is Not Required for Proliferation or Functional Telomere Maintenance in Chicken DT40 Cells

Carol Cooley^*, Katie M. Baird, Virginie Faure^*, Thomas Wenner^*, Jillian L. Stewart, Sonie Modino, Predrag Slijepcevic, Christine J. Farr, and Ciaran G. Morrison^*

*Centre for Chromosome Biology, National University of Ireland Galway, Department of Biochemistry and NCBES, Galway, Ireland; Department of Genetics, University of Cambridge, Cambridge CB2 3EH, United Kingdom; and Brunel Institute of Cancer Genetics and Pharmacogenomics, Brunel University, Uxbridge, Middlesex UB8 3PH, United Kingdom

Submitted October 14, 2008; Revised February 23, 2009; Accepted March 16, 2009
Monitoring Editor: Wendy Bickmore

The telomere end-protection complex prevents the ends of linear eukaryotic chromosomes from degradation or inappropriate DNA repair. The homodimeric double-stranded DNA-binding protein, Trf1, is a component of this complex and is essential for mouse embryonic development. To define the requirement for Trf1 in somatic cells, we deleted Trf1 in chicken DT40 cells by gene targeting. Trf1-deficient cells proliferated as rapidly as control cells and showed telomeric localization of Trf2, Rap1, and Pot1. Telomeric G-strand overhang lengths were increased in late-passage Trf1-deficient cells, although telomere lengths were unaffected by Trf1 deficiency, as determined by denaturing Southern and quantitative FISH analysis. Although we observed some clonal variation in terminal telomere fragment lengths, this did not correlate with cellular Trf1 levels. Trf1 was not required for telomere seeding, indicating that de novo telomere formation can proceed without Trf1. The Pin2 isoform and a novel exon 4, 5–deleted isoform localized to telomeres in Trf1-deficient cells. Trf1-deficient cells were sensitive to DNA damage induced by ionizing radiation. Our data demonstrate that chicken DT40 B cells do not require Trf1 for functional telomere structure and suggest that Trf1 may have additional, nontelomeric roles involved in maintaining genome stability.

Address correspondence to: Ciaran G. Morrison (ciaran.morrison{at}nuigalway.ie)

Abbreviations used: DSB, DNA double-strand break; ES cell, embryonic stem cell; MEF, murine embryonic fibroblast; PNA, peptide nucleic acid.

This article has been cited by other articles:

				P. Spallarossa, P. Altieri, C. Aloi, S. Garibaldi, C. Barisione, G. Ghigliotti, G. Fugazza, A. Barsotti, and C. Brunelli Doxorubicin induces senescence or apoptosis in rat neonatal cardiomyocytes by regulating the expression levels of the telomere binding factors 1 and 2 Am J Physiol Heart Circ Physiol, December 1, 2009; 297(6): H2169 - H2181. [Abstract] [Full Text] [PDF]