Telomere Maintenance Requires the RAD51D Recombination/Repair Protein

The five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are required in mammalian cells for normal levels of genetic recombination and resistance to DNA-damaging agents. We report here that RAD51D is also involved in telomere maintenance. Using immunofluorescence labeling, electron micros...

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Bibliographic Details
Published in:Cell 2004-04, Vol.117 (3), p.337-347
Main Authors: Tarsounas, Madalena, Muñoz, Purificacı́on, Claas, Andreas, Smiraldo, Phillip G, Pittman, Douglas L, Blasco, Marı́a A, West, Stephen C
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - metabolism
Blotting, Western
Cell Line, Transformed
Cell Transformation, Neoplastic
Chromatin - metabolism
Chromosome Aberrations
DNA Damage
DNA Repair
DNA, Cruciform - metabolism
DNA, Cruciform - ultrastructure
DNA-Binding Proteins - metabolism
DNA-Binding Proteins - ultrastructure
Fibroblasts - metabolism
HeLa Cells
Humans
In Situ Hybridization, Fluorescence
Male
Mice
Mice, Knockout
Precipitin Tests
Recombination, Genetic
RNA, Small Interfering - metabolism
Spermatocytes - metabolism
Spermatocytes - ultrastructure
Telomere - metabolism
Telomeric Repeat Binding Protein 2 - metabolism
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Summary:The five RAD51 paralogs (RAD51B, RAD51C, RAD51D, XRCC2, and XRCC3) are required in mammalian cells for normal levels of genetic recombination and resistance to DNA-damaging agents. We report here that RAD51D is also involved in telomere maintenance. Using immunofluorescence labeling, electron microscopy, and chromatin immunoprecipitation assays, RAD51D was shown to localize to the telomeres of both meiotic and somatic cells. Telomerase-positive Rad51d−/− Trp53−/− primary mouse embryonic fibroblasts (MEFs) exhibited telomeric DNA repeat shortening compared to Trp53−/− or wild-type MEFs. Moreover, elevated levels of chromosomal aberrations were detected, including telomeric end-to-end fusions, a signature of telomere dysfunction. Inhibition of RAD51D synthesis in telomerase-negative immortalized human cells by siRNA also resulted in telomere erosion and chromosome fusion. We conclude that RAD51D plays a dual cellular role in both the repair of DNA double-strand breaks and telomere protection against attrition and fusion.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(04)00337-X