Nucleic Acids Research, 2002, Vol. 30, No. 13 2862-2870
© 2002 Oxford University Press
Effects of double-strand break repair proteins on vertebrate telomere structure
Department of Molecular Genetics, Biochemistry and Microbiology, College of Medicine, University of Cincinnati, ML0524, 231 Albert Sabin Way, Cincinnati, OH 45267, USA, 1 Department of Veterinary Science, University of Nebraska, Lincoln, NE 68588, USA, 2 Department of Immunology and Molecular Genetics, Kawasaki Medical School, Okayama 701-0192, Japan and 3 Department of Radiation Genetics, Faculty of Medicine, Kyoto University, Kyoto 606-8501, Japan
Although telomeres are not recognized as double-strand breaks (DSBs), some DSB repair proteins are present at telomeres and are required for telomere maintenance. To learn more about the telomeric function of proteins from the homologous recombination (HR) and non-homologous end joining pathways (NHEJ), we have screened a panel of chicken DT40 knockout cell lines for changes in telomere structure. In contrast to what has been observed in Ku-deficient mice, we found that Ku70 disruption did not result in telomeretelomere fusions and had no effect on telomere length or the structure of the telomeric G-strand overhang. G-overhang length was increased by Rad51 disruption but unchanged by disruption of DNA-PKcs, Mre11, Rad52, Rad54, XRCC2 or XRCC3. The effect of Rad51 depletion was unexpected because gross alterations in telomere structure have not been detected in yeast HR mutants. Thus, our results indicate that Rad51 has a previously undiscovered function at vertebrate telomeres. They also indicate that Mre11 is not required to generate G-overhangs. Although Mre11 has been implicated in overhang generation, overhang structure had not previously been examined in Mre11-deficient cells. Overall our findings indicate that there are significant species-specific differences in the telomeric function of DSB repair proteins.
* To whom correspondence should be addressed. Tel: +1 513 558 0450; Fax: +1 513 558 8474; Email: carolyn.price{at}uc.edu
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