BOR - Papers in Press, published online ahead of print
October 23, 2002.
Biol Reprod 2002, 10.1095/biolreprod.102.008672
BIOLOGY OF REPRODUCTION 68, 628634 (2003)
DOI: 10.1095/biolreprod.102.008672
© 2003 by the Society for the Study of Reproduction, Inc.
DNA Double-Strand Breaks and
-H2AX Signaling in the Testis1
Geert Hamer2,a,b,
Hermien L. Roepers-Gajadiena,b,
Annemarie van Duyn-Goedhartd,
Iris S. Gademanc,
Henk B. Kalc,
Paul P.W. van Buuld, and
Dirk G. de Rooija,b
a Department of Endocrinology, Faculty of Biology, Utrecht University, 3584 CH Utrecht, The Netherlands
b Departments of Cell Biology
c Radiotherapy, UMCU, 3584 CX Utrecht, The Netherlands
d MCG-Department of Radiation Genetics and Chemical Mutagenesis, Sylvius Laboratory, Leiden University, 2333 AL Leiden, The Netherlands
Within minutes of the induction of DNA double-strand breaks in somatic cells, histone H2AX becomes phosphorylated at serine 139 and forms
-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
-H2AX foci appear in response to irradiation and genotoxic stress and during V(D)J recombination and meiotic recombination. Independent of irradiation,
-H2AX occurs in all intermediate and B spermatogonia and in preleptotene to zygotene spermatocytes. Type A spermatogonia and round spermatids do not exhibit
-H2AX foci but show homogeneous nuclear
-H2AX staining, whereas in pachytene spermatocytes
-H2AX is only present in the sex vesicle. In response to ionizing radiation,
-H2AX foci are generated in spermatogonia, spermatocytes, and round spermatids. In irradiated spermatogonia,
-H2AX interacts with p53, which induces spermatogonial apoptosis. These events are independent of the DNA-dependent protein kinase (DNA-PK). Irradiation-independent nuclear
-H2AX staining in leptotene spermatocytes demonstrates a function for
-H2AX during meiosis.
-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
-H2AX foci at DNA double-strand breaks.
1 This work was supported by the J.A. Cohen Institute for Radiopathology and Radiation Protection, Leiden, The Netherlands.
2 Correspondence: Geert Hamer, Department of Endocrinology, Faculty of Biology, Utrecht University, Padualaan 8, 3584 CH Utrecht, The Netherlands. FAX: 31 30 2532837; g.hamer{at}bio.uu.nl
Copyright © 2003 by the Society for the Study of Reproduction.