Role of mammalian Rad54 in telomere length maintenance.
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.
Jaco
Isabel
I
Department of Immunology and Oncology, Centro Nacional de Biotecnología, Madrid E-28049, Spain.
Muñoz
Purificación
P
Goytisolo
Fermín
F
Wesoly
Joanna
J
Bailey
Susan
S
Taccioli
Guillermo
G
Blasco
María A
MA
D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004265:DNA Helicases; D004260:DNA Repair; D045643:DNA Repair Enzymes; D005838:Genotype; D006579:Heterozygote; D017404:In Situ Hybridization, Fluorescence; D051379:Mice; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000235:genetics*
D029701:Saccharomyces cerevisiae Proteins; D019098:Telomerase; C075468:RAD54 protein, S cerevisiae; D004265:DNA Helicases; D045643:DNA Repair Enzymes