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Molecular and Cellular Biology, August 2003, p. 5572-5580, Vol. 23, No. 16
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.16.5572-5580.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Role of Mammalian Rad54 in Telomere Length Maintenance

Isabel Jaco,1 Purificación Muñoz,1 Fermín Goytisolo,1 Joanna Wesoly,2 Susan Bailey,3 Guillermo Taccioli,4 and María A. Blasco1*

Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain,1 Department of Genetics, Erasmus University, Rotterdam, The Netherlands,2 Department of Radiological Health Sciences, Colorado State University, Fort Collins, Colorado 80523,3 Department of Microbiology, Boston University School of Medicine, Boston, Massachusetts 021184

Received 24 February 2003/ Returned for modification 4 April 2003/ Accepted 20 May 2003

The homologous recombination (HR) DNA repair pathway participates in telomere length maintenance in yeast but its putative role at mammalian telomeres is unknown. Mammalian Rad54 is part of the HR machinery, and Rad54-deficient mice show a reduced HR capability. Here, we show that Rad54-deficient mice also show significantly shorter telomeres than wild-type controls, indicating that Rad54 activity plays an essential role in telomere length maintenance in mammals. Rad54 deficiency also resulted in an increased frequency of end-to-end chromosome fusions involving telomeres compared to the controls, suggesting a putative role of Rad54 in telomere capping. Finally, the study of mice doubly deficient for Rad54 and DNA-PKcs showed that telomere fusions due to DNA-PKcs deficiency were not rescued in the absence of Rad54, suggesting that they are not mediated by Rad54 activity.

* Corresponding author. Mailing address: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain. Phone: 34-915854846. Fax: 34-913720493. E-mail: mblasco{at}cnb.uam.es.

Molecular and Cellular Biology, August 2003, p. 5572-5580, Vol. 23, No. 16
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.16.5572-5580.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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