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Abstract
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.
ACKNOWLEDGMENTS
We thank R. Serrano and E. Santos for mouse care and genotyping.
I.J. is a predoctoral fellow of Gulbenkian Foundation (Portugal), and P.M. is a Ramón y Cajal Senior Scientist. Research at the laboratory of M.A.B. is funded by grant PM97-0133 from the MCYT, grant 08.1/0030/98 from CAM, and grants EURATOM/991/0201, FIGH-CT-1999-00002 and FIS5-1999-00055 from the European Union and by the DIO. The DIO was founded and is supported by the Spanish Research Council (CSIC) and by Pharmacia. G.T. is a scholar of the Leukemia and Lymphoma Society. The G.T. laboratory is supported by National Institutes of Health (NIH) grant CA76409 and the Human Frontier Science Program. The S.B. laboratory is supported by grants from the U.S. Department of Energy (ER632339) and the NIH (CA43322).