DNA Double-Strand Breaks and (gamma)-H2AX Signaling in the Testis

Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated at serine 139 and forms (gamma)-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 (gamma)-H2AX foci appear in response to irradiation and genotoxic stress and during V(D)J recombination and meiotic recombination. Independent of irradiation, (gamma)-H2AX occurs in all intermediate and B spermatogonia and in preleptotene to zygotene spermatocytes. Type A spermatogonia and round spermatids do not exhibit (gamma)-H2AX foci but show homogeneous nuclear (gamma)-H2AX staining, whereas in pachytene spermatocytes (gamma)-H2AX is only present in the sex vesicle. In response to ionizing radiation, (gamma)-H2AX foci are generated in spermatogonia, spermatocytes, and round spermatids. In irradiated spermatogonia, (gamma)H2AX interacts with p53, which induces spermatogonial apoptosis. These events are independent of the DNA-dependent protein kinase (DNA-PK). Irradiation-independent nuclear (gamma)-H2AX staining in leptotene spermatocytes demonstrates a function for (gamma)-H2AX during meiosis. (gamma)-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 (gamma)-H2AX foci at DNA double-strand breaks.