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Rad54/Rad54B deficiency is associated to increased chromosome breakage in mouse spermatocytes

TitleRad54/Rad54B deficiency is associated to increased chromosome breakage in mouse spermatocytes
Publication TypeArticolo su Rivista peer-reviewed
Year of Publication2018
AuthorsRusso, A., Cordelli Eugenia, Salvitti T., Palumbo E., and Pacchierotti Francesca
Keywordsanimal, animal experiment, Animals, article, chromosome, Chromosome aberration, chromosome breakage, Chromosomes, comparative study, controlled study, deficiency, DNA Breaks, DNA helicase, DNA Helicases, DNA repair, double stranded DNA break, Double-Stranded, genetics, histone H2AX, Karyotype, Knockout, knockout mouse, male, meiosis, metabolism, Metaphase, Mice, micronucleus test, mouse, nonhuman, nuclear protein, Nuclear Proteins, nucleic acid binding protein, priority journal, protein function, protein phosphorylation, Rad54 protein, rad54b protein, Rad54l protein, Radiation Tolerance, seminiferous tubule, spermatid, spermatocyte, Spermatocytes, spermatogenesis, structural chromosome aberration, unclassified drug

Rad54 protein is a key player of the homologous recombination pathway, required for deposition and stabilisation of Rad51 foci at double strand breaks. Its role at the meiotic prophase, when double strand breaks are physiologically introduced to allow recombination, is well described. However, the hypothesis that Rad54 deficiency affect chromosome integrity of germ cells in unirradiated and irradiated animals has not been tested yet. In this study, the occurrence of spontaneous and X-ray-induced chromosome aberrations was assessed by analysis of spermatocyte MI spreads or by application of micronucleus assay in early spermatids isolated from wild type and Rad54/Rad54B knockout (KO) mice. In Rad54/Rad54B KO mice, the spontaneous chromosome aberration frequency detected at MI was >10-fold higher than in wild type animals. In addition, after exposure to 1 Gy X-rays at the radiosensitive stage of diplotene, an enhanced response to radiation was observed in Rad54-deficient animals, corresponding to a 2-3 sensitivity factor in comparison to wild type mice. Also the spontaneous frequency of micronucleated round spermatids was on the average 10-fold higher in KO than in wild type mice, indicating that Rad54/Rad54B KO spermatocytes carrying chromosome aberrations are able to pass through the meiotic divisions and to continue the spermatogenesis process. Our results provide the first evidence of the role of Rad54/Rad54B in the maintenance of a stable karyotype during male meiosis, and suggest that Rad54/Rad54B deficiency may impact on the DNA integrity of developing mouse gametes.


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Citation KeyRusso2018323