Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

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.

Type

Journal article

Journal

Cell

Publication Date

30/04/2004

Volume

117

Pages

337 - 347

Keywords

Animals, Antibodies, Monoclonal, Blotting, Western, Cell Line, Transformed, Cell Transformation, Neoplastic, Chromatin, Chromosome Aberrations, DNA Damage, DNA Repair, DNA, Cruciform, DNA-Binding Proteins, Fibroblasts, HeLa Cells, Humans, In Situ Hybridization, Fluorescence, Male, Mice, Mice, Knockout, Precipitin Tests, RNA, Small Interfering, Recombination, Genetic, Spermatocytes, Telomere, Telomeric Repeat Binding Protein 2