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1 February 2003 DNA Double-Strand Breaks and γ-H2AX Signaling in the Testis
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Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated at serine 139 and forms γ-H2AX foci at the sites of damage. These foci then play a role in recruiting DNA repair and damage-response factors and changing chromatin structure to accurately repair the damaged DNA. These γ-H2AX foci appear in response to irradiation and genotoxic stress and during V(D)J recombination and meiotic recombination. Independent of irradiation, γ-H2AX occurs in all intermediate and B spermatogonia and in preleptotene to zygotene spermatocytes. Type A spermatogonia and round spermatids do not exhibit γ-H2AX foci but show homogeneous nuclear γ-H2AX staining, whereas in pachytene spermatocytes γ-H2AX is only present in the sex vesicle. In response to ionizing radiation, γ-H2AX foci are generated in spermatogonia, spermatocytes, and round spermatids. In irradiated spermatogonia, γ-H2AX interacts with p53, which induces spermatogonial apoptosis. These events are independent of the DNA-dependent protein kinase (DNA-PK). Irradiation-independent nuclear γ-H2AX staining in leptotene spermatocytes demonstrates a function for γ-H2AX during meiosis. γ-H2AX staining in intermediate and B spermatogonia, preleptotene spermatocytes, and sex vesicles and round spermatids, however, indicates that the function of H2AX phosphorylation during spermatogenesis is not restricted to the formation of γ-H2AX foci at DNA double-strand breaks.

Geert Hamer, Hermien L. Roepers-Gajadien, Annemarie van Duyn-Goedhart, Iris S. Gademan, Henk B. Kal, Paul P. W. van Buul, and Dirk G. de Rooij "DNA Double-Strand Breaks and γ-H2AX Signaling in the Testis," Biology of Reproduction 68(2), 628-634, (1 February 2003).
Received: 25 June 2002; Accepted: 1 August 2002; Published: 1 February 2003

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