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.
Hamer
Geert
G
Department of Endocrinology, Faculty of Biology, Utrecht University, 3584 CH Utrecht, The Netherlands. g.hamer@bio.uu.nl
Roepers-Gajadien
Hermien L
HL
van Duyn-Goedhart
Annemarie
A
Gademan
Iris S
IS
Kal
Henk B
HB
van Buul
Paul P W
PP
de Rooij
Dirk G
DG
D000818:Animals; D004247:DNA; D004249:DNA Damage; D004260:DNA Repair / Q000502:physiology; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins; D006657:Histones / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016513:Mice, SCID; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013090:Spermatocytes / Q000378:metabolism; D013093:Spermatogonia / Q000378:metabolism; D013737:Testis / Q000378:metabolism / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology; D014916:Whole-Body Irradiation
D004268:DNA-Binding Proteins; C468783:H2AX protein, human; D006657:Histones; D016159:Tumor Suppressor Protein p53; C475961:gamma-H2AX protein, mouse; D004247:DNA; D051747:DNA-Activated Protein Kinase; D017346:Protein Serine-Threonine Kinases